Long-term treatment with luspatercept-aamt (Reblozyl) elicited the longest duration of reduced red blood cell (RBC) transfusion dependence among patients with β-thalassemia, according to updated data from the phase 3 BELIEVE trial (NCT02604433), presented at the 2022 EHA Congress.

Response was assessed as reduction of RBC transfusion burden by at least 33% from baseline and by at least 50% from baseline among patients who received luspatercept vs placebo during any rolling 12- or 24-week interval. With a long-term data cutoff of January 5, 2021, among the 224 patients in the luspatercept arm, 173 patients (77.2%) had at least 33% response during any 12-week interval and 116 (51.8%) had a response during any 24-week interval. A transfusion burden reduction of at least 50% was reported among 112 patients (50%) and 53 patients (23.7%) during any 12- and 24-week interval, respectively.

These outcomes were compared with prior data cutoff landmarks: May 11, 2018 (primary data cutoff) and January 7, 2019 (intermediate data cutoff). In the primary analysis, 70.5% and 41.1% of patients had at least a 33% reduction in transfusion burden at the 12- and 24-week intervals. These rates were 76.3% and 45.1% in the intermediate analysis, respectively. Reduction of at least 50% were reported at any 12- and 24-week intervals among 40.2% and 16.5% of patients, respectively, in the primary analysis and 44.6% and 20.5% in the intermediate analysis.

“In terms of transfusion independence, at the cutoff of 3 years 12% of patients [who received] luspatercept, achieved transfusion independence, equal to or more than [8] weeks. And that, of course, implies the longest interval of this condition of transfusion in dependence,” said Maria Domenica Cappellini, MD, FRCP, FACP, professor of internal medicine at the University of Milan and chief of the Rare Diseases Centre at the Fondazione IRCCS Policlinico Hospital in Italy, during a presentation of the data.

The median longest duration of RBC transfusion independence was 72 days (95% CI, 62-103) with longer-term luspatercept treatment. At the primary and intermediate analysis cutoffs, the rates of RBC transfusion independence lasting at least 8 weeks were 10.7% and 11.2%, respectively, compared with 12.1% in the longer-term analysis.

“Continuous treatment with the luspatercept allowed for more patients to experience a reduction in RBC transfusion burden, with longer durations of responses compared [with] the previous cutoff,” Cappellini said. “We are confident that these [benefits] will be even more clear with longer follow-up and patients with transfusion dependent β-thalassemia treated in the BELIEVE study will continue to benefit from luspatercept with over 3 years of treatment.”

Additional data showed that the median duration of RBC transfusion burden reduction was 114 days (95% CI, 107-137) and 99 days (95% CI, 95-104) for those with 33% reduction and 50% reduction, respectively, at the long-term analysis cutoff. In the primary data cutoff analysis, the median duration of RBC transfusion burden reduction was 104 days (95% CI, 84-588) for those with at least 33% reduction and 97.5 days (95% CI, 84-588) for those with at least 50% reduction. In the intermediate analysis the median duration was 105 days (95% CI, 84-825) and 99 days (95% CI, 84-825), respectively.

The median treatment duration during the primary, intermediate, and long-term landmark analyses were 64.1 days (95% CI, 3-97), 95.7 days (95% CI, 1.7-128.1), and 153.6 days (95% CI, 1.7-215).

Further, the mean cumulative duration of RBC transfusion burden reduction during any rolling 12-week interval was 627.3 (standard deviation, 390.5) for patients who received luspatercept.

In terms of RBC transfusion burden change from baseline, Cappellini noted that patients receiving luspatercept required fewer units of blood over time. The mean change in RBC units every 48 weeks from baseline was –4.8 (weeks 1-48), –5.6 (weeks 49-96), –6.2 (weeks 97-144), and –6.4 (weeks 145-192) compared with a 1.1 unit increase reported in weeks 1-48 with placebo.

Cappellini also highlighted that patients achieving an RBC transfusion burden reduction of 50% or higher experienced a greater interval between the transfusions compared with the baseline over time at a mean of +9.9 days (standard deviation, 22.0).

Luspatercept, an erthyroid maturation agent, is approved for the treatment of anemia in patients with β-thalassemia who require regular red blood cell (RBC) transfusions. Additionally, it received an indication for patients who require 2 or more RBC units over 8 weeks for patients with very low- to intermediate-risk myelodysplastic syndromes (MDS) with ring sideroblasts or with MDS/myeloproliferative neoplasm with ring sideroblasts and thrombocytosis.

BELIEVE was a randomized, double-blind, study comparing luspatercept with placebo.

 Investigators enrolled adults with β-thalassemia who required regular transfusions of 6 to 20 RBC units in the 24 weeks prior to random assignment, with no transfusion-free period (35 days). Patients were randomly assigned 2:1 to luspatercept (n = 224) plus best supportive care or placebo plus best supportive care (n = 112). Luspatercept was administered subcutaneously 1.0 mg/kg (up to a maximum dose of 1.25 mg/kg) every 3 weeks. Best supportive care included RBC transfusions to maintain baseline hemoglobin levels and iron chelation therapy.

The primary end point was reduction of RBC transfusion burden by at least 33% from baseline with a reduction of at least 2 units in weeks 13 to 24 compared with the 12 weeks prior to randomization.

Baseline characteristics between the experimental and control arm were well balanced. The median age was 30 years (range, 18-66). Median hemoglobin levels at 24 weeks were 9.31 g/dL (range, 4.5-11.4) and 9.15 g/dL (range, 5.8-11.7) in the luspatercept arm and placebo arm, respectively. The median RBC transfusion burden was 6.12 units (range, 3-14) every 12 weeks in the luspatercept arm and 6.27 (range, 3-12) in the placebo arm. The median burden every 24 weeks was 14 units (range, 6-24) and 15 (range, 6-26), respectively. Further, over half of patients (57.6% and 58.0%, respectively) had a splenectomy.

In terms of liver iron concentration (LIC), at baseline the median LIC in the luspatercept arm was 6.4 mg/g dry weight (range, 0.8-125.0) and 5.05 mg/g dry weight (range, 0.2-53.2) in the placebo arm. An analysis of LIC is ongoing, according to Cappellini.

At data cutoff 127 patients (56.7%) remained on study treatment and 2.7% (n = 6) have completed 192 weeks of treatment. Of the 224 patients in the luspatercept arm, 96 (42.9%) discontinued treatment. The most common reasons for discontinuation were physician decision (23.7%), adverse event (10.3%), or other (5.4%).

Cappellini MD, Taher AT, Porter JB, et al. Longer-term analysis of efficacy of luspatercept in patients with transfusion-dependent β-thalassemia enrolled in the BELIEVE study. Presented at: 2022 EHA Congress; June 9-17, 2022; Vienna, Austria. Abstract S270.

Reblozyl. Prescribing information. Celegene; 2020. Accessed June 11, 2022. bit.ly/3c0E2sj

An efficacy and safety study of luspatercept (ACE-536) versus placebo in adults who require regular red blood cell transfusions due to beta (β) thalassemia (BELIEVE). ClinicalTrials.gov. Updated January 25, 2022. Accessed June 11, 2022. 

https://clinicaltrials.gov/ct2/show/NCT02604433

Articles

Updated data from the phase 3 BELIEVE trial revealed a sustained reduction in the need for red blood cell transfusions among patients with β-thalassemia who received treatment with luspatercept-aamt.

Luspatercept Linked With Maintained Reduction in Transfusion Dependence Among Patients With β-Thalassemia

Viable long-term responses with tisagenleleucel (Kymriah) were observed among pediatric and young adult patients with heavily pretreated relapsed or refractory B-cell acute lymphoblastic leukemia (B-ALL), according to a 5-year follow-up of the phase 2 ELIANA trial (NCT02435849) presented at the 2022 EHA congress.

Among 79 patients, with a median age of 11 years (range, 3-24), the overall remission rate (ORR) was 82% with a complete remission (CR) rate of 62% and a CR with incomplete blood count recovery (CRi) rate was 20%. Additionally, 98% of patients who achieved remission had minimal residual disease (MRD) negativity at 3 months.

Among 65 responders, the median relapse-free survival (RFS) was 43 months (95% CI, 12- not estimable [NE]). The 5-year RFS rate was 44% (95% CI, 31%-56%).

“Long term remission rates up to 5.9 years of follow up from ELIANA demonstrate that tisagenlecleucel may be a curative treatment option for heavily pretreated pediatric and young adult patients with relapsed or refractory B-ALL,” Susana Rives, MD, PhD, said in a presentation of the data. Rives is a specialist physician in the Pediatric Oncology Department of Sant Joan de Déu Barcelona Children’s Hospital and head of the Hematopoietic System Tumors Unit at the Sant Joan de Déu Hospital, in Spain.

ELIANA enrolled patients with relapsed or refractory B-cell ALL between the ages of 3 and 21 years with bone marrow lymphobasts of at least 5% who had not received prior CD19-directed therapy. Patients received lymphodepleting chemotherapy prior to infusion comprising 30 mg/m2 of intravenous (IV) fludarabine daily for 4 doses with cyclophosphamide 500 mg/m2 IV daily for 2 doses.

Patients proceeded to a single infusion of tisagenlecleucel based on weight at the time of infusion. For patients weighing over 50 kg, the dose range was 0.1 to 2.5 × 108 cells and for those weighing 50 kg or less the dose range was 0.2 to 5.0 × 106 cells. The primary end point was ORR within 3 months, and 4-week maintenance of remission by independent review committee assessment. Secondary end points included MRD status, duration of response, RFS, event-free survival (EFS), overall survival (OS), cellular kinetics, and safety.

At baseline, the median number of prior lines of therapy was 3 (range, 1-8) and 61% of patients has prior allogeneic stem cell transplantation (alloSCT). Most patients had primary refractory disease status (92%) and the median morphologic blast count in bone marrow was 74% (range, 5%-99%).

At the time of last evaluation, 31 patients were in remission with a median follow-up of 60.1 months (range, 25.3-68.5).

The median EFS was 15 months (95% CI, 10-45) with a 5-year EFS rate of 36% (95% CI, 25%-47%). When censoring for patients who underwent alloSCT the median EFS was 13 months (95% CI, 9-35) with a 5-year EFS rate of 34% (95% CI, 23%-45%).

Further, at the time of the final analysis the median OS was not reached (95% CI, 46- NE). At 5 years, 55% of patients were alive (95% CI, 43%-66%).

Investigators reported that the probability of B-cell aplasia was 83% (95% CI, 71%-91%) at 6 months and 71% (95% CI, 57%-82%) at 12 months. The median time to B-cell recovery was 39 months and among those who achieved B-cell recovery the cumulative incidence of relapse was 40%.

Following infusion with tisagenlecleucel, 25% of patients underwent alloSCT. Investigators noted that 4 patients had alloSCT within 3 months of receiving the CD19-directed CAR T-cell therapy. In total, 10 patients underwent transplant in remission and 7 had alloSCT and the remaining 14 underwent transplant after 3 months.

Investigators noted that results for OS and EFS between pediatric (< 18 years) vs young adult patients (≥ 18 years) were comparable. Among 65 pediatric patients the median OS was not reached (95% CI, 44-NE) vs 57 months (95% CI, 10-NE) among 14 young adult patients. The median EFS was 15 months for both populations.

Rives noted that no new long-term treatment-related safety events were reported in the long-term analysis. Adverse effects of special interest (AESIs) observed after 1 year post infusion were reported at the meeting.

Among patients who achieved remission at any time during the study, including those who received a response at any time (n = 70), 39% had at least 1 AESI of any grade and 21% had an AESI grade 3 or higher.

The most commonly reported AESI was infection with any-grade incidence of 33% and grade 3 or higher incidence reported among 20% of patients. All-grade hemaphagocytic lymphohistiocytosis or cytokine release syndrome was reported in 1 patient and was grade 3 or higher. Serious neurologic events occurred in 3% of patients with 1 event grade 3 or higher. Hematological disorders, including cytopenias, were reported in 10% of patients, and 4 events were grade 3 or higher.

“We had a patient with a secondary malignancy—a myelodysplasia—this patient had a prior [allogeneic] transplant with [total body irradiation] TBI and with and high cumulative doses of etoposide, cyclophosphamide, and tricyclines, but still she had moderate cytopenias with severe dysplastic signs in peripheral blood and bone marrow,” Rives said adding that the patient received no further therapy and the cytopenias are stable.

A majority of patients (82%) received immunoglobulin IV at any time post infusion with 33% of patients receiving the infusion after 1 year and 16% after 2 years. Further, 88% of patients in remission received immunoglobulin IV during persistent B-cell aplasia.

Tisagenlecleucel was approved for use in pediatric and young adult patients with B-ALL in 2017 based on earlier data from the ELIANA study.2 In data that led to the approval, the ORR was 83% (95% CI, 71%-91%) among 63 evaluable patients and the median duration of remission was not reached. MRD negativity was reported in all responders.

Rives S, Maude AL, Hiramatsu H, et al. Tisagenlecleucel in pediatric and young adult patients with relapsed/refractory B-cell acute lymphoblastic leukemia: final analyses from the ELIANA study. Presented at: 2022 EHA Congress. June 9-17, 2022; Vienna, Austria. Abstract S112.

FDA approves tisagenlecleucel for B-cell ALL and tocilizumab for cytokine release syndrome. FDA. Updated September 7, 2017. Accessed June 13, 2022. bit.ly/3aWMs6o

Heavily pretreated pediatric and young adult patients with relapsed or refractory B-cell acute lymphoblastic leukemia maintained response with tisagenlecelucel according to long-term follow-up data from the phase 2 ELIANA trial. 

Pediatric/Young Adult Patients With B-ALL Continue to Derive Benefit From Tisagenlecluecel at 5-Year Follow-Up

Data from the phase 3 Children’s Oncology Group (COG) Protocol AAML1031 (NCT01371981) demonstrated that sorafenib (Nexavar) when added to conventional chemotherapy offers a safe and effective strategy for pediatric patients with 

-ITD–positive acute myeloid leukemia (AML), according to findings published in the 

Treatment with sorafenib was associated with improved event-free survival (EFS) from study entry (

 = .001) as well as disease-free survival (DFS; 

 = .032) and relapse risk from complete remission (CR; 

 = .012) but not overall survival (OS; 

The median follow-up time for patients alive at last contact was 5.3 years (range, 0.3-13.1). There were 32 EFS events among patients who received sorafenib (n = 72) and 35 events among patients who did not (n = 76).

“These data demonstrate that sorafenib dosing of 200 mg/m2 [per] day was tolerable in conjunction with conventional chemotherapy, significantly improved EFS, relapse risk, and DFS, and provided potent FLT3 inhibition,” lead study author Jessica A. Pollard, MD, a physician at Dana-Farber Cancer Institute, and coauthors wrote in the publication. “For treatment of pediatric 

-ITD–positive AML outside of a study context, these data provide compelling support for sorafenib combined with conventional chemotherapy.”

-ITD mutations are associated with poor prognosis in pediatric AML, but chemotherapy remains the standard of care. Prior studies have shown sorafenib is safe in adults with 

-mutant AML. Following documentation of sorafenib’s ease of administration in the pediatric population, investigators sought to examine its use in combination with chemotherapy.

The study enrolled 1645 patients with newly diagnosed, 

-ITD–mutant AML, of which 1609 were eligible. Patients were randomized to 1 of 4 arms: standard chemotherapy consisting of asparaginase, cytarabine, daunorubicin, and etoposide (arm A); asparaginase, bortezomib (Velcade), cytarabine, daunorubicin, and etoposide (arm B); asparaginase, cytarabine, daunorubicin, etoposide, and sorafenib (arm C); or cytarabine, daunorubicin, and etoposide (arm D).

At enrollment, patients were randomized to arm A or arm B and underwent centralized 

-ITD mutation testing. Patients with a high 

-ITD allelic ratio (> 0.4) were eligible for enrollment on arm C, which was split into 3 cohorts. If consented, patients initially randomized to arm A continued standard chemotherapy with sorafenib, and patients in arm B discontinued bortezomib when consenting to arm C. After arms A and B closed, 19 patients were enrolled on arm D until 

-ITD results returned; if positive, patients were eligible for arm C.

Of the 1609 patients enrolled, 8.5% (n = 136) had high allelic ratio 

-ITD–positive AML and were eligible for enrollment in arm C, of which 68% (n = 92) of patients consented. Another 42 patients with high allelic ratio enrolled on arm A or B did not participate in arm C.

During the safety phase, sorafenib was given at a dose of 200 mg/m2 once daily; this dose was determined to be the recommended dosing for sorafenib given the absence of protocol defined dose-limiting toxicities requiring treatment de-escalation. Following completion of the first cohort, the study was amended such that cohort 2 started sorafenib on day 11 of induction 1 and received the agent concomitantly with chemotherapy thereafter.

A preliminary signal of increased cardiac toxicity was reported in 22% (n = 7) of patients in cohort 2 of arm C as defined by grade 3 ejection fraction decline (n = 3), grade 2 ejection fraction decline (n = 2), grade 3 left-ventricular systolic dysfunction (n = 1), grade 2 cardiac other (shortening fraction decline, n = 1), and grade 1 cardiac other (shortening fraction decline, n = 1).

Two patients met the criteria for permanent discontinuation of sorafenib and both tolerated restart. The remaining five discontinued treatment before retreatment was possible. This safety signal led investigators to start sorafenib after completion of standard chemotherapy in each cycle.

A year of sorafenib maintenance, administered after hematopoietic stem cell transplant (HSCT) or completion of chemotherapy was added for patients enrolled in cohort 2 given early evidence of the activity of maintenance therapy. Maintenance dosing was 100 mg/m2 daily with a potential for escalation to a maximum dose of 150 mg/m2 twice daily.

Only 80 patients received sorafenib maintenance in cohorts 2 and 3 of arm C; 38% (n = 30) received at least 1 cycle and 25% (n = 20) completed all maintenance treatment. Maintenance toxicity rates were comparable to those of earlier treatment cycles.

Additional findings from secondary analyses, in which patients who were sorafenib-treated and -naïve were censored at the date of last contact, demonstrated similar outcomes as did censoring of both groups at the time of elective withdrawal.

-positive tumors treated with sorafenib did not show a statistically significant improvement in outcomes vs those who did not receive sorafenib (EFS: 

Although outcomes appeared better overall for children with 

-ITD–positive AML who received sorafenib, they also underwent HSCT more frequently than the comparator population (64% vs 25%, respectively; 

 status and HSCT as a time-varying covariate, significantly worse EFS, DFS, and relapse risk was seen in patients who did not receive sorafenib vs those who did (EFS from study entry: HR, 2.37; 95% CI, 1.45-3.88;

 < .001; DFS from CR: HR, 2.28; 95% CI, 1.08-4.82; 

 = .032; relapse risk from CR: HR, 3.03; 95% CI, 1.31-7.04; 

In terms of safety, dose-limiting toxicities reported in cohort 1 of arm C included rash (grade 2, n = 1; grade 3, n = 1), grade 2 hand-foot syndrome (n = 1), and grade 3 fever (n = 1). The incidence of targeted toxicities was comparable between all 3 cohorts of arm C.

Patients initially enrolled on arm A before switching to arm C (n = 53) were compared with patients who remained on arm A (n = 34). Targeted toxicities were comparable overall as well as across cohorts and treatment phases for patients in arm C who initially were treated on arm A. Additionally, the incidence of chemotherapy-related dose reduction and intensive care unit admission were similar. Notably, patients in arm C were more likely to receive dexrazoxane as a cardioprotectant with anthracycline therapy during induction (

 = .006). No significant unanticipated toxicities were reported in the sorafenib cohort.

Ultimately, the cardiac toxicity reported in arm C was similar to that of arm A. Differences in median ejection fraction were also similar between arms C and A and across arm C cohorts.

“These data are the largest analysis of sorafenib efficacy in pediatric 

-ITD–positive AML. The presently open COG phase 3 study, AAML1831 [NCT04293562], builds on our sorafenib experience by testing gilteritinib in both 

-ITD–positive AML and children with clinically relevant 

-activating mutations,” the study authors concluded.

Pollard JA, Alonzo TA, Gerbing R, et al. Sorafenib in combination with standard chemotherapy for children with high allelic ratio FLT3/ITD+ acute myeloid leukemia: a report from the Children's Oncology Group Protocol AAML1031. 

. Published online March 29, 2022. doi:10.1200/JCO.21.01612

Bortezomib and sorafenib tosylate in treating patients with newly diagnosed acute myeloid leukemia. ClinicalTrials.gov. Updated April 29, 2022. Accessed June 1, 2022. https://clinicaltrials.gov/ct2/show/NCT01371981

This article was originally published on 

® as “Sorafenib Plus Standard Chemotherapy Provides Clinical Benefit in Pediatric 

Standard chemotherapy plus sorafenib achieved clinical benefit in pediatric patients with FLT3-ITD–positive acute myeloid leukemia.

Addition of Sorafenib to Chemotherapy Found to be Safe, Effective in Pediatric FLT3-ITD+ AML

, we spoke with Donna Herrera Bell, MSN, APRN, FNP-C, an oncology nurse practitioner with The University of Texas MD Anderson Cancer Center (MD Anderson) who spent 14 years working with children and adolescents with leukemia and lymphoma as well as helped develop a Pediatric Onco-Fertility consult service with MD Anderson.

Bell recently presented at the 47th Annual Oncology Nursing Society Congress about eliminating barriers to conversations around fertility preservation for adolescent or young adult patients with cancer. In our discussion, Bell highlights common barriers that young men and women face, reasons why oncology nurses may not always feel comfortable addressing the topic of fertility, and why initiating the conversation and raising fertility risk awareness is crucial following a cancer diagnosis.

“Fertility preservation is not something that everyone can do. But it is something that every [patient should] discuss, and feel empowered about,” Bell says.

, please consider subscribing to our podcast on Apple Podcasts, Spotify, Google Podcasts, Amazon Music, and many of your other favorite podcast platforms, to get a notification every time a new episode is posted. While you are there, please take a moment to rate us!

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In this episode of The Vitals, Donna Herrera Bell, MSN, APRN, FNP-C, highlights how nurses can eliminate barriers to fertility discussions among adolescent and young adult patients with cancer.

Improving Onco-Fertility Conversations With Adolescents and Young Adult Patients With Cancer

Receiving a cancer diagnosis is less common for adolescents or young adult (AYA) compared with young children or older adults. AYA patients often report that when they look around the waiting room at their treatment center, or even in their local patient support group, they tend to see patients either half or double their age. This experience can result in feelings of isolation, anxiety, and depression.

COVID-19 quarantine mandates exacerbated these emotions by forcing AYA patients, an already underrepresented population within the cancer community, to physically isolate, cutting them off from the few resources that were available to them. This lack of peer support resulted in many AYAs relying on alternative ways to connect with one another, such as social media.

In the past decade, there has been a significant rise in the use of social media. Apps like Facebook, Instagram, and TikTok, have continued to garner attention over the years, but over the course of pandemic, these platforms became even more important. Many individuals turned to these platforms to stay connected when they could not physically see family and friends. Social media apps proved to be a place of community for many— particularly for AYA patients navigating a cancer diagnosis.

A recent study completed by Memorial Sloan Kettering Cancer Center set out to identify the primary needs unique to AYAs throughout their cancer care experience. The participants of the study were between the ages of 15 and 39 and had been treated in either MSKCC’s medical or pediatric oncology unit. The results of the study revealed that the most common theme amongst the participants was the feeling of social isolation and the desire to connect with peers throughout the course of their care.

 A participant recounted how a friend, who had undergone leukemia treatment in her twenties, was surprised to hear someone else her age was similarly diagnosed. Her experience had felt so isolating. ‘You are the only other person I’ve ever met who is my age who has gone through something like this,’ she had said. Unfortunately, this experience is incredibly common. There are very few treatment centers that offer resources, groups, or programs dedicated to AYA patients. Furthermore, at the time of a cancer diagnosis, AYA patients are typically at the point in their life cycle in which they are completing their education, becoming independent, engaging in self-discovery, and starting a career or a family of their own. It is difficult to navigate these milestones under normal circumstances—when these changes are combined with the challenges of a cancer diagnosis, the result is a unique experience that can only be understood by other AYA patients in this position.

Social media created a platform for AYAs navigating these specific challenges to share their experiences, emotions and perspectives in a way that hasn’t been done before. Users are given the opportunity to disclose their diagnosis story, their experiences with healthcare, side effects of treatment, survivorship, confronting their mortality and many more topics. Most importantly, by using hashtags such as #Cancer or #AYACancer on Twitter or #Cancertok on TikTok, AYA patients are able to attract other users that these hashtags might apply to. As an AYA cancer patient, finding someone on social media that is going through something similar can significantly reduce feelings of isolation and reiterate that they are not alone.

Kasey Altman, a 26-year-old that was diagnosed with Stage 4 Rhapdomyosarcoma in 2020, has accumulated 58.3K followers on TikTok since she decided to share her story. She has gained her following by posting candidly about her metastatic diagnosis, raising awareness about the unique challenges associated with AYA cancer, and engaging in advocacy efforts. Her posts highlight the ups and downs of treatment, managing side effects, and self-care tips for those that are newly diagnosed. When asked about how social media has impacted the AYA cancer community, Kasey stated, “My main thoughts are centered on how excruciating it is to suffer in silence. TikTok makes it less lonely. It's a community filled with fiercely loyal followers and people who seem to genuinely care about the well-being of others.” This kind of support, empathy and level of understanding is crucial to healthy coping.

In another study, the use of social media was explored in the advanced cancer experiences among AYA patients. It was determined that digital technologies have been used as a primary means of support. Participants of the study, ages 14-25, indicated that social media and the use of video games allowed them to meet others who are facing similar challenges. It also allowed for them to stay connected with friends who they might not be able to see in person as a result of treatment.

 These types of connections are integral, especially for individuals that might be immunocompromised. Many AYAs receive their treatment in-patient, or even have to stay in the hospital for weeks at a time if they are recovering from a procedure like a stem cell transplant. AYAs also need the same access to support after completing treatment. A common misconception is that once treatment ends, life picks back up as normal. However, that is far from the truth. Adjusting to post treatment is actually when the peer connection is most important.

Julie Kramer, a 31-year-old that was diagnosed with stage 4 Synovial Sarcoma in 2014, stated, “Instagram became a huge resource for me during, but mainly after, cancer to find fellow AYA patients who not only had the same cancer, but more importantly related to such similar struggles as I did and currently do. I cannot express how helpful it is to my mental health and well-being having the online cancer community as an outlet to meet, engage and vent to fellow patients and survivors.” Having access to social media creates a pathway to connection, even if patients are physically alone while in treatment or are navigating post treatment.

Social media and public disclosure are not for everyone and that is also okay. Many AYAs report that social media can actually increase feelings of isolation and sadness when they see posts from healthy peers going about their day to day lives. It is essential to encourage patients to check-in with themselves prior to engaging in social media activity to ensure that it is the right source of support and connection for them. It might also be helpful for patients to set boundaries around their social media use to ensure it is used appropriately and productively. If there are in-person or virtual AYA specific groups or programs offered at one’s treatment center, it can be helpful to supplement both sources of support.

If an AYA patient you know is in need of support, please call CancerCare’s HOPEline to speak with an oncology social worker at (800) 813-4673. Cancer

 offers free emotional support services, limited financial assistance, case management, educational programs and workshops for individuals impacted by cancer, but particularly for AYA patients.

Atkinson T, Avutu V, Barnett M, Glade Bender J, Lynch K, Tap W, Vera J. Psychosocial needs and preferences for care among adolescent and young adult cancer patients (ages 15-39): a qualitative study. 

Barton K, Frazier J, Rosenberg A, Steineck A, Walsh C. Seeking virtual support: social media in the advanced cancer experience among adolescents and young adults. 

https://doi.org/10.1016/j.jpainsymman.2021.01.102

The rise of social media platforms has helped foster a community for adolescent and young adult patients with cancer.

How Social Media Helps AYA Patients With Cancer Find Support

The FDA has approved azacitidine (Vidaza) to treat pediatric patients with newly diagnosed juvenile myelomonocytic leukemia (JMML).

The regulatory decision is supported by data from the international, multicenter, open-label AZA-JMML-001 (NCT02447666), in which investigators examined the safety and efficacy of azacitidine vs historical controls in pediatric patients with newly diagnosed myelodysplastic syndrome or JMML before hematopoietic stem cell transplantation (HSCT).

A total of 18 study participants were administered intravenous azacitidine at a daily dose of 75 mg/m2 on days 1 through 7 of a 28-day treatment cycle for a minimum of 3 cycles and a maximum of 6 cycles. The primary end point of the trial was response rate, which was comprised of complete remission (cCR) or clinical partial remission (cPR) per International JMML response criteria, at 3 months.

Results showed that 50% of patients (95% CI, 26%-74%) experienced confirmed clinical responses with the drug. Of these patients, 3 achieved a cCR and 6 experienced a cPR.

Moreover, the median time to response was 1.2 months (range, 0.95-1.87). Ninety-four percent of patients went on to receive HSCT, and the median time to transplant was 4.6 months (range, 2.8-19).

Prior data indicated that 38% of those who required platelet transfusion were free of transfusion following the third cycle of therapy. Of the 17 patients who went on to undergo HSCT, 82% were leukemia free at a median follow-up of 23.8 months (range, 7.0-39.3).

Regarding safety, the most common effects included pyrexia, rash, upper respiratory tract infection, and anemia.

FDA approves azacitidine for newly diagnosed juvenile myelomonocytic leukemia. News release. FDA. May 20, 2022. Accessed May 23, 2022. https://bit.ly/3Lt1VrL

Niemeyer CM, Flotho C, Lipka DB, et al. Response to upfront azacitidine in juvenile myelomonocytic leukemia in the AZA-JMML-001 trial. 

. 2021;5(14):2901-2908. doi:10.1182/bloodadvances.2020004144

Azacitidine (Vidaza) is now FDA approved for pediatric patients with newly diagnosed myelomonocytic leukemia.

FDA Grants Azacitidine Approval For Pediatric Patients With Myelomonocytic Leukemia

Oncology nurses can serve as the key to ensure that cancer survivors receive the follow-up care they need, according to Michelle Mollica, PhD, MPH, RN, OCN.

Mollica, who is a senior advisor in the NCI Office of Cancer Survivorship and is consequently responsible for developing, supporting, and promoting research efforts focused on cancer survivorship, presented on individualized survivorship care plans at the 47th Annual Oncology Nursing Society Congress. During the meeting, she sat down with Oncology Nursing News® to discuss what nurses should know about survivorship care plans.

“Something I cannot stress enough is the importance of the oncology nurse in assessing the specific needs of cancer survivors and that [this] needs to happen early,” Mollica said. “Listen and be aware of what patients and survivors need from the point of diagnosis all the way through because those needs might change.”

 Could you discuss the basic framework of an effective survivorship care plan?

: A survivorship care plan is a tool that is meant to guide patients and survivors, as well as health care providers, for the necessary survivorship care. Ideally, the plan should have a summary of cancer history, pertinent health history, as well as treatment summaries, and a follow-up plan for what should occur in the future for that survivor. It should be tailored to the needs of the survivor, and their cancer type and treatment history.

How might care for a childhood cancer survivor differ from that of an adult or even an elderly patient?

Individuals who are diagnosed with cancer as children are at high risk for late- and long-term effects—symptoms that occur well after their treatment has ended. There is a real need to monitor for those impacts, especially things like cardiotoxicity and other symptoms, well after their treatment has ended.

That is different from an older adult who often is dealing with lots of other comorbid conditions: they might have diabetes or have other health issues that are in essence competing with their follow-up care for cancer. It is up to the older adult to coordinate their care in a way with their providers that makes the most sense based on their needs.

What are the challenges in caring for different populations, specifically rural cancer survivors?

Rural cancer survivors often have issues engaging and accessing survivorship care; they are less likely to receive a survivorship care plan or have a survivorship care discussion with their oncologist. They often have challenges engaging back with their primary care provider after their treatment has ended or knowing what types of treatment follow-up care they need.

Oncology nurses play a key role in sort of bridging that gap. They can help survivors know what's ahead, know how to access those resources, and [guide them through] supported self-management—[teaching] when to call if they have symptoms or issues that they think they may need to get checked out. The oncology nurse is key to both assessing the needs of survivors and educating patients, particularly for vulnerable populations like rural cancer survivors.

Which factors do you consider when determining a patient's level of risk?

Many professional organizations have recommended risk-based survivorship care, which means that survivorship care is tailored based on the needs of the survivor. That can include an assessment of factors that include risk for recurrence risk for second cancers, their likelihood for late- and long-term effects, and how many other comorbid conditions they have. It can also be based on things like level of social support: do they have someone to take them to their follow-up care visits? It is important to [consider these risks] and tailor the care based on these factors.

What are some challenges that can be linked to primary care coordination? How might a nurse help overcome those barriers?

Primary care providers are dealing with so many things daily. Seeing cancer survivors is just a small part of their day, although we have a growing number of survivors that are being seen in primary care. When survivors are transitioned back to primary care, either during or after treatment, it is essential that primary care providers know what type of care is needed and how to deliver that care for the survivor. I would say there are lots of challenges to doing that.

Engaging with primary care and having access to a primary care provider is always a challenge. In addition, primary care providers often need to be educated on the impact of new therapies like biotherapies and targeted therapies—these may have another host of symptoms that survivors need to worry about, as well as staying up with guidelines for cancer survivors.

Oncology nurses can help survivors navigate those challenges. They can help educate patients and what they should bring to their primary care provider. They can also make contact with the primary care provider and in many cases, advanced practice oncology nurse practitioners are actually providing that survivorship care and bridging that gap.

How can patients be proactive in helping to manage their care plans or even coordinating with their care team to individualize it?

It is important for patients to know what questions need to be asked and to ask as many questions as early and often as possible. That includes: what type of care do I need to receive? What is this going to look like for me as I transition either off treatment, or in these periods where I might not be treated? Who should I see and when, and making sure that that's all included in their survivorship care plan and using that as a tool to navigate their care?

Patients also need to be empowered to reach out if they experience any symptom that they aren't familiar with or is new to them. This is because, often, symptoms emerge that we might not be aware of between visits, and they need to know to reach out to their provider and ask questions.

Michelle Mollica, PhD, MPH, RN, OCN, senior advisor in the NCI Office of Cancer Survivorship, discusses different long-term care considerations for nurses caring for patients with cancer. 

Oncology Nurses Play Pivotal Role in Survivor Follow-Up Care

Female cancer survivors are as likely to give birth to healthy babies as women who were not treated for cancer, according to a study recently published in the 

Journal of the National Cancer Institute.

 However, female cancer survivors are more likely to develop a severe complication during pregnancy or labor than those without a history of cancer, the data caution.

Findings showed that female cancer survivors were just as likely as the general female population to carry a pregnancy past 20 weeks (relative risk [RR] = 1.01; 95% CI, 0.98-1.04) and that there was no difference in birth defects or Agpar scores between babies born in the survivor or control group cohorts.

Among more than 4000 cancer survivors, only 87 women (2%) experienced a serious complication during labor or developed a heart problem during pregnancy. Furthermore, cancer survivors were twice as likely to experience these difficulties compared with non-cancer survivors.

At 30 years old, women who had survived cancer had a cumulative incidence of achieving a recognized pregnancy of 22.3% (95% CI, 20.7%-23.9%) compared with 26.6% (95% CI, 25.6%-27.3%) among the general population (HR, 0.80; 95% CI, 0.75-0.86). Risk factors for a lower likelihood of conception included history of a brain tumor, alkylator chemotherapy, cranial radiation, or hematopoietic stem cell transplantation (HSCT).

“The message here is largely positive,” said study leader Paul Nathan, MD, of the Hospital for Sick Children in Toronto, Canada. “Women who have a history of childhood cancer have a really good chance of getting pregnant, and most of them are quite fine through the pregnancy. But it’s super important for the people caring for them to know about these risks.”

Investigators identified 4062 women who had underwent cancer therapy between 1985 and 2012 while they were under the age of 21 years. All evaluable patients were identified via a single-payer health insurance program covering Ontario, Canada. Each patient with a history of cancer was compared with 5 women with no history of cancer. In total, the survivors were compared against 20,308 comparisons women from the general population, totaling in an assessment of over 24,000 women.

Although women who had received treatment were just as likely to give birth to a healthy baby as women from the general population, they were at an increased risk of severe maternal morbidity (RR, 2.31; 95% CI, 1.59-3.37), cardiac morbidity (RR, 4.18; 95% CI, 1.89-9.24), and preterm birth (RR, 1.57; 95% CI, 1.29-1.92). Furthermore, patients who had received allogenic HSCT were more likely to experience a preterm birth (RR, 8.37; 95% CI, 4.83-14.48) as did those who underwent autologous transplant (RR, 3.72; 95% CI, 1.66-8.35).

These results suggest that female cancer survivors may benefit from high-risk obstetric care, although in the United States, ensuring that survivors know to seek these resources could be improved through better communication between providers, noted experts.

“High-risk obstetric care is widely available in most of the country, but childhood cancer survivors may not be recognized as needing that kind of care,” Emily Tonorezos, MD, director of NCI’s Office of Cancer Survivorship, commented on the study. Tonorezos noted that health care providers may not know that their patient was treated for cancer as a child, particularly if they have relocated between cities or states and transferred to a new medical system.

“The burden of making sure you’re getting good health care is very often on the survivor and their family,” added Tonorezos. “That’s not where the burden should be, but survivors need to [make sure] health care providers have some of that information, because sharing data is not built into our health system,” she added.

Nathan agreed that women who were treated for cancer before the age of 21 would benefit from frank conversations with their providers about a potential need for high-risk obstetric care. This high-risk care could encompass heath monitoring throughout pregnancy, as well as frequent fetal monitoring. The key, according to Nathan, will be ensuring that all the providers caring for a childhood cancer survivor understand their medical history.

“Health care providers’ knowledge of a patient’s cancer history can also spur other important conversations about reproductive health,” he said. “[Figuring out] how to share this information with health care providers is going [to be] one of our key goals.”

Overall, however, these findings are promising for cancer survivors, as they suggest that a healthy pregnancy is possible with a little additional monitoring, concluded experts. “The expectation of a healthy pregnancy and a healthy baby should be the norm, even for childhood cancer survivors,” said Tonorezos.

1. Zgardau A, Ray JG, Baxter NN, et al. Obstetrical and perinatal outcomes in female survivors of childhood and adolescent cancer: a population-based cohort study. Published online ahead of print January 19, 2022. 

2. NCI Staff. Good News and cautions about pregnancy for childhood cancer survivors. National Cancer Institute. March 4, 2022. Accessed March 28, 2022. https://bit.ly/3iJyGoA

Childhood cancer survivors may benefit from high-risk obstetric care despite being able to conceive and give birth safely. 

Childhood Cancer Survivors Likely to Deliver Healthy Babies, But May Require Additional Monitoring During Pregnancy 

Further research is still required to determine the optimal timing, frequency, and intensity of physical activity for childhood cancer survivors, according to findings from a comprehensive literature review that was published in 

Notably, the review concluded that regular physical activity is linked to a decreased risk of cardiovascular disease and all-cause mortality among childhood cancer survivors. Increased neurocognition is an added benefit of participating in exercise. However, because different cancer therapies are linked to varying amounts cardiovascular tissue damage and impacted regenerative potential, the extent to which exercise and health are linked may greatly differ between survivors.

“Our review shows that modifiable lifestyle choices, including PA [physical activity], are likely effective in improving physical fitness and reducing the risk for future organ dysfunction,” Chelsea Goodenough, PhD, Epidemiology and Cancer Control Department, St Jude Children’s Research Hospital, and colleagues, explained in the study.

“Most research has been focused on improving physical fitness to [cardiovascular disease] risk, due to its association with early mortality in childhood cancer survivors. However, because childhood cancer survivors are also at increased risk for early onset endocrine, musculoskeletal, and severe neurological disorders, and because PA and associated gains in physical fitness mitigates risk for these diseases in other populations, observational and interventional work is needed to determine if increasing PA and improving physical fitness decreases the risk of future chronic disease in childhood cancer survivors.”

Currently, the 5-year survival rate associated with childhood cancer is greater than 80%; recent advancements in pediatric oncology have emphasized the need for better survivorship care plans. Unfortunately, frailty is observed at a higher rate among childhood cancer survivors than among their non-survivor peers. The rate of frailty among young adults who have survived cancer is comparable with that of adults in the general population over the age of 70 (7.9% vs 9.9%, respectively). Frailty is linked to a 2.2% increased risk of chronic disease (95% CI, 1.2-4.2), and consequently, childhood cancer survivors, on average, face 7.27 chronic health conditions (95% CI, 7.26-8.18). Frailty is also linked to an increased mortality risk among survivors (HR, 2.6; 95% CI, 1.2-6.2).

Exercise and physical activity have been shown to improve physical fitness and physiologic reserve, making it a prevention and mitigation method for frailty. Physical fitness is defined as the ability to “carry out daily tasks without undue fatigue” and is considered a physiological adaptation.

In March 2020, researchers conducted a comprehensive literary review, which included studies published in PubMed, Web of Science, Cumulative Index to Nursing and Allied Health Literature, and Cochrane databases via Ovid.

Searched keywords included “survivor” and “childhood cancer,” or “survivor” and “neoplasms” and “child.” These terms were cross referenced with the following keywords: “physical activity” or “exercise” or “exercise therapy” or “exercise tolerance” or “physical exertion” or “physical fitness” and “chronic disease” or “organ dysfunction” or “late effect” or “mortality.” In addition to all papers flagged by the previously mentioned keywords, researchers also reviewed the reference sections listed with relevant papers.

Overall, 595 studies were assessed, and 11 study results were presented in the review. Researchers concluded that survivors who regularly exercised had both improved markers of cardiovascular health and a decreased risk of overt cardiovascular disease, as well as a decreased risk of all-cause mortality, in comparison with their peers who do not regularly exercise.

“For survivors of childhood cancer, low physiological reserve may limit healthy, physiological adaptation from repeated bouts of PA, thus, increasing the risk of age-related chronic diseases. However, this does not mean that childhood cancer survivors should not engage in exercise,” the authors summarized. “The current literature demonstrates that survivors who engage in PA, even if they have past exposure to cardiotoxic therapies, have reduced risk of adverse cardiac outcomes.”

The authors concluded that more studies are needed to determine the most effective interventions—such as intervention timing, behavioral strategies, delivery mechanisms, and exercise dose—to improve physical fitness in survivors to a point where it would have an impact on chronic disease risk.

Wogksch D, Goodenough CG, Finch ER, et al. Physical activity and fitness in childhood cancer survivors: a scoping review. 

 2021;2(4):112-128. doi:10.1002/aac2.12042

A comprehensive literature review underscores research gaps into optimal exercise regimens for childhood cancer survivors. 

Nuanced Research Needed on the Value of Exercise for Childhood Cancer Survivors

As an oncology nurse, it can be easy to get lost in a feeling of guilt when someone in your life receives a cancer diagnosis, according to Janice Post-White, PhD, RN, FAAN. However, it is important to acknowledge that guilt before one can let it go.

Post-White was an oncology nurse when her 4-year-old son, Brennan, was diagnosed with B-cell acute lymphoblastic leukemia. Her recently published book, “Standing at Water’s Edge,” delves into the fear and grief she felt while her son was undergoing treatment.

s®, Post-White explained how, after her son’s diagnosis, she struggled with a heavy feeling of guilt for not recognizing the signs sooner. She went on to explain that many people may deal with similar feelings of guilt, but that the important thing is to recognize it to move forward.

“You reflect back, and you [wonder] how did I miss that?” explained Post-White.

“We can we ruminate about the past, we [can] worry about the future, but the important thing is to stay present in the day,” she continued. “Guilt is an incredible burden—and all of those ‘would haves—should haves—could haves’, [or however] you think about, [or thinking] ‘I should have done 

. Why didn't I see that?’ It is a burden to carry.”

“It is important to acknowledge it and say, ‘I feel guilty about this. I need to process this before I can let it go.’ Writing helped me do that. But that's what you need to do. You need to process it and you need to feel it again before you can let it go,” she concluded.

Videos

Janice Post-White, PhD, RN, FAAN, an oncology nurse and caregiver, discusses how she handled the guilt she felt following her son’s leukemia diagnosis. 

Childhood/AYA Cancer