Patients with cancer who have non-O blood types may be at a time-dependent increased risk of venous thromboembolism (VTE), according to results of a study published in 

Specifically, patients in this population are an increased risk once they reach 3 months of follow-up, and among patients with intermediate- and low-risk tumor types.

Overall, at a median follow-up time of 24 months (interquartile range, 10-24), 151 patients with cancer developed VTE out of 1708 evaluable patients (8.8%). There was no reported association between non-O blood type and VTE risk observed within the first 3 months of follow-up (sub-distribution hazard ration [SHR], 1.00; 95% CI, 0.60-1.67).

However, beyond that time marker, a connection between the adverse event (AE) and the factor began to emerge (SHR, 1.79; 95% CI, 1.12-2.85). Notably, the association was only present in patients with intermediate- and low-thrombotic risk tumor types (SHR 1.73; 95% CI, 1.09-2.73), but not in high-risk tumor types such as pancreatic, gastroesophageal, and brain cancer (SHR 0.94; 95% CI, 0.55-1.61).

“In this prospective observational cohort study, we have shown that ABO  blood type is associated with risk of VTE in patients with cancer in a time-dependent manner,” the study authors wrote. “These results indicate that cancer may be the main driver of the increased risk of VTE shortly after diagnosis or progression, depicting a time when the cancer is very active and patients are receiving anti-cancer therapies, putting them at high risk for VTE. This time period is also the one with the highest incidence of VTE in patients with cancer.”

Patients with cancer are 5-9 times more likely to experience VTE and VTE among this population is associated with poor prognoses; in addition, routine thromboprophylaxis is not recommended for these patients because they are at an increased risk of bleeding. Since the general population has non-O blood types, researchers sought to understand the relationship between this event and ABO blood types.

“Current guidelines recommend pharmacological thromboprophylaxis in patients with high VTE risk that are most likely to benefit,” the authors noted. “Therefore, better understanding of risk profiles and identification of simple risk factors contributing to elevated risks of VTE is desired to aid in clinical decision making.”

Investigators conducted an analysis with the Vienna Cancer and Thrombosis Study (CATS)– a prospective cohort study which evaluated patient with newly diagnosis or recurrent cancer. Investigators performed restricted cubic spline analysis and specific time-restricted subdistribution hazard ratios to determine the association between non-O blood type and VTE over time.

Eligible patients were older than 18 years, had histologically confirmed cancer, and were either newly diagnosed or had disease progression following partial or complete remission.

Patients were ineligible if they had received chemotherapy or experienced VTE in the last 3 months, or had long-term anticoagulation, overt viral or bacterial infection, radiotherapy, or surgery 2 weeks prior to study inclusion.

Patient were followed for 2 years and contacted via postal mail and phone to gather information about their clinical outcomes. If patients did not respond, their family doctor or relatives were contacted.

At a median follow-up of 24 months, the 3-, 6-, 12-, and 24-month cumulative VTE occurrences were 3.6% (95% CI, 2.7-4.5), 6.2% (95% CI, 5.1-7.5), 7.8% (95% CI, 6.6-9.2) and 9.2% (95% CI, 7.9-10.7), respectively. A total of 649 deaths occurred throughout the 2-year observation period with a 2-year mortality rate of 38%.

Among the 1708 patients included in the study, 794 were female (46%) and the median age was 61 years (interquartile range, 52-68 years). Lung cancer represented the most common tumor type (19%), and was closely followed by breast cancer (16%) and brain cancer (14%). At the study inclusion, 32% of patients with solid tumors presented metastatic disease.

Among the ABO blood types included in the study, 653 (38%) were blood type O, 682 were type A (40%), 262 were type B (15%), and 111 were type AB (7%), which is typical of a European population.

ABO blood group distribution was not varied across patients with different tumor types and corresponding tumor risk categories. In addition, there was no association between having stage 3 disease at study inclusion and belonging to either blood group O versus non-O. No association between ABO blood type group and survival was observed.

Overall, the findings suggest “that non-O blood type acts as a putative predictor of VTE in patients with cancer at comparatively low risk of thrombosis,” the authors concluded. “ABO blood type group is an easily accessible VTE predictor that can help in the clinical practice during risk assessment in patients with cancer.”

Englisch C, Moik F, Nopp S, Raderer M, Pabinger I, Ay C. ABO blood group type and risk of venous thromboembolism in patients with cancer. 

. Published online April 13, 2022. doi:10.1182/bloodadvances.2021006283.

Articles

New research suggests that blood type may be an easily accessible predictor of venous thromboembolism risk.

 Non-O Blood Types May Be Linked to Venous Thromboembolism in Patients With Cancer

The addition of ublituximab and umbralisib (Ukoniq; U2) to ibrutinib (Imbruvica) demonstrated a 77% undetectable minimal residual disease (uMRD) rate in patients with chronic lymphocytic leukemia (CLL), along with a tolerable safety profile, according to phase 2 results presented at the 47th Annual Oncology Nursing Society (ONS) Congress.

“This novel patient care approach of ‘add-on’ combination therapy was well tolerated and effective, with achievement of uMRD in 77% of evaluable patients allowing for tailored, time-limited therapy and sustained treatment-free observation,” lead study author Colleen Dorsey, RN, BSN, of Memorial Sloan Kettering Cancer Center, and coinvestigators wrote in the poster presented during the meeting. “This approach may assist nurses with patient care challenges such as management of adverse events due to indefinite ibrutinib therapy.”

The findings with this combination mirror what was presented during the 2021 ASH Annual Meeting. In the phase 2 trial (NCT04016805), the addition of U2 to ibrutinib led to a 77% uMRD rate in this patient population.

 Moreover, 4% of patients came off treatment after 24 cycles and continued to have detectable MRD.

Time-limited therapy has shown efficacy in the form of high and durable response rates in previous data; however, this approach has also been linked with an increase in adverse effects (AEs) as well as a risk of overtreatment, the authors noted.

In the data presented at the ONS Congress, investigators utilized an “add-on” and MRD-driven, time-limited treatment approach with U2 following single-agent ibrutinib. To be eligible for enrollment, patients had to be receiving ongoing ibrutinib for at least 6 months and have detectable MRD.

In addition to ibrutinib, umbralisib was administered orally at 800 mg daily and ublituximab was given intravenously on days 1 and 2 at a split dose of 150 mg and 750 mg, and then at 900 mg total on days 8 and 15 of cycle 1, day 1 of cycles 2 through 6, and on day 1 every 3 cycles after cycle 6.

Following confirmation of uMRD, patients were entered into a treatment-free observation. For those who did not have a confirmed uMRD, patients continued therapy for up to 24 cycles followed by a treatment-free observation.

Outcome measures included uMRD rate, safety, and duration of clinical benefit after treatment discontinuation.

Of the 27 evaluable patients, the median age was 64 years and 79% of patients were male. The median time to first uMRD was 7.4 months (95% CI, 4.6-20.2) and 77% of patients had at least 1 uMRD assessment.

Sixteen patients (67%) entered TFO and were off therapy for a median of 242 days off treatment (range, 5-538). TFO appeared durable and at the last follow-up, 73% of these patients remained in uMRD. Retreatment was not required in any patients per International Workshop on CLL criteria.

Regarding safety, the triplet regimen was well tolerated. Overall all-causality grade 3/4 AEs of special interest included hypertension (7%), alanine aminotransferase/aspartate aminotransferase increase (4%), COVID-19 (4%), and diarrhea (4%). There were 2 treatment discontinuations due to rash (n = 1) and rash plus arthralgia (n = 1); however, both patients were in uMRD at the time of treatment discontinuation and remain in uMRD.

These results follow the April 2022 announcement that the pending biologics license application (BLA) and supplemental new drug application (sNDA) seeking the approval of the combination of ublituximab and umbralisib in adult patients with CLL and small lymphocytic lymphoma (SLL) had been voluntarily withdrawn by the developer of U2, TG Therapeutics, Inc.

The decision follows updated overall survival data yielded from the phase 3 UNITY-CLL trial (NCT026112311), which demonstrated an increasing imbalance in survival in favor of the control arm.

TG Therapeutics also announced the decision to voluntarily withdraw umbralisib from sale for the approved indications of adult patients with marginal zone lymphoma (MZL) who have previously received at least 1 anti–CD20-based regimen and for adult patients with follicular lymphoma who previously received at least 3 systemic therapies.

The FDA granted an accelerated approval to umbralisib in February 2021 for these indications based on data from 2 single-arm cohorts of the open-label, multicenter, phase 2/3 UNITY-NHL trial (NCT02793583).

 Results showed that the objective response rate was 49% (95% CI, 37.0%-61.6%) in patients with MZL (n = 69), which included a complete response (CR) rate of 16%. The ORR achieved with the agent in patients with follicular lymphoma (n = 117) was 43% (95% CI, 33.6%-52.2%), which included a CR rate of 3%.

Dorsey C, Falco V, Pena-Velasquez CP, et al. A phase 2 study evaluating the addition of ublituximab and umbralisib (U2) to ibrutinib in patients with chronic lymphocytic leukemia (CLL): a minimal residual disease (MRD)-driven, time-limited approach. Presented at: 47th Annual Oncology Nursing Society Congress; April 27-May 1, 2022; Anaheim, CA. Abstract P303.

Roeker LE, Leslie LA, Soumerai JD, et al. A phase 2 study evaluating the addition of ublituximab and umbralisib (U2) to ibrutinib in patients with chronic lymphocytic leukemia (CLL): a minimal residual disease (MRD)-driven, time-limited approach. Blood. 2021;138(suppl 1):395. doi:10.1182/blood-2021-146999

TG Therapeutics announces voluntary withdrawal of the BLA/sNDA for U2 to treat patients with CLL and SLL. News release. TG Therapeutics, Inc.; April 15, 2022. Accessed April 15, 2022. https://bit.ly/36lqqZm

FDA grants accelerated approval to umbralisib for marginal zone lymphoma and follicular lymphoma. News release. FDA; February 5, 2021. Accessed April 15, 2021. http://bit.ly/3aCBqQa

The addition of ublituximab and umbralisib (Ukoniq; U2) to ibrutinib (Imbruvica) demonstrated a 77% undetectable minimal residual disease (uMRD) rate in patients with chronic lymphocytic leukemia.

 Time-Limited Ublituximab/Umbralisib Plus Ibrutinib Shows Efficacy, Tolerability in CLL

Very low dose radiation therapy (VLDRT) was found to be an effective treatment approach in the palliative setting for patients with indolent non-Hodgkin lymphoma, but it is not considered a standard of care in this patient population, according to findings presented at the 47th Annual Oncology Nursing (ONS) Congress.

Additionally, a benefit of VLDRT is that it allows retreatment to the same field as needed. While radiation-related toxicities were low in both VLDRT and standard radiation (RT) therapy groups, the shorter treatment schedule of 2 treatments vs 12 treatments is also a quality-of-life benefit in the palliative setting.

Preparation for either radiation dosing approach, as well as the timetable of scans to determine response to treatment, remains the same.

The goal of the research was to close the gap in oncology nursing literature and define the role of VLDRT in patients with indolent lymphomas, Catherine Adams, BSN, RN, OCN, of Memorial Sloan Kettering Cancer Center, and coinvestigators, wrote in the poster presentation.

“Standard treatment can be started immediately if VLDRT is not effective for control of localized disease,” the authors wrote. “VLDRT does not compromise future types of treatment.”

Indolent lymphomas, specifically follicular lymphomas and marginal zone lymphomas, are known to be very radiosensitive. Historically, patients with these malignancies have been treated with radiation doses at 40 Gy to 45 Gy for a total of 20 treatments.

Previous research has shown that 24 Gy for 12 treatments was also found to be effective for disease control in patients with localized follicular lymphoma.2 Additionally, data from the FORT trial (NCT00310167), which compared the use of 24 Gy with 4 Gy, showed that 24 Gy should be standard of care, though 4 Gy remains an optimal alternative in the palliative setting.3

In the poster presented at the ONS Congress, the authors noted that the preparation for VLDRT is the same as standard 24 Gy. They also referred to retrospective data from 1994 to 2017,4 which compared the early and late toxicities of patients who received standard vs VLDRT to nonorbital head and neck fields, which included the oral cavity, nasal cavity, salivary glands, sinuses, Waldeyer’s ring, and nodal disease.

The retrospective findings showed that the toxicities rates were significantly lower for the nonorbital head fields with VLDRT (n = 17) vs standard radiation (RT; n = 51) regarding dermatitis, xerostomia, dysgeusia, mucositis, esophagitis, site pain, anorexia, nausea, alopecia, dysphagia, and edema.

The findings were similar for the neck field for those who received VLDRT (n = 18) vs standard RT (n = 80); rates of dermatitis, xerostomia, esophagitis, dysphagia, hoarseness, mucositis, dysgeusia, alopecia, and nausea were all lower with 4 Gy.

Further patient benefits of VLDRT include “decreased time requirements for the patient to complete treatment, decreased disruption to patient/family life and work schedule, and decreased financial burden related to travel cost, child-care expenses, and potential loss of work for patient and/or family members,” the authors concluded in the poster.

Adams C, Cho G, Yahalom J, et al. "Boom-Boom" very low dose, 2 fraction radiation therapy for the treatment of indolent non-Hodgkin lymphoma in the palliative setting. Presented at: 47th Annual Oncology Nursing Society Congress; April 27-May 1, 2022; Anaheim, CA. Abstract P6.

Lowry L, Smith P, Qian W, et al. Reduced dose radiotherapy for local control in non-Hodgkin lymphoma: a randomised phase III trial. 

. 2011;100(1):86-92. doi:10.1016/j.radonc.2011.05.013.

Hoskin PJ, Kirkwood AA, Popova B, et al. 4 Gy versus 24 Gy radiotherapy for patients with indolent lymphoma (FORT): a randomised phase 3 non-inferiority trial. 

. 2014;15(4):457-63. doi: 10.1016/S1470-2045(14)70036-1.

Chelius M, Chau K, Yang J, et al. Low grade, indolent lymphomas of the head and neck: Comparative toxicity of standard versus very low dose radiation therapy. 

. 2021;39(3):304-312. doi:10.1002/hon.2865

Very low dose radiation therapy was found to be an effective treatment approach in the palliative setting for patients with indolent non-Hodgkin lymphoma.

Very Low-Dose RT Is Effective, Although Not Standard in Indolent Non-Hodgkin Lymphoma

Ilene Galinsky, BSN, MSN, ANP-C, senior leukemia protocol research nurse practitioner, at Dana Farber Cancer Institute, discusses how treatment for patients with acute myeloid leukemia (AML) has evolved in recent years.

It is a very exciting to be a nurse or nurse practitioner in oncology, Galinksy explained, especially with the advances in therapeutics for patients with AML. These novel therapies are now less toxic compared with 7+3 chemotherapy, which patients would previously receive regardless of their molecular makeup. 

The evolution in science has also led to identification of molecular abnormalities and ways to target these aberrations through treatment, Galinsky explains. These precision medicine approaches have led to improvements in overall survival as well as quality of life, she concludes. 

Videos

Ilene Galinsky, BSN, MSN, ANP-C, senior leukemia protocol research nurse practitioner, at Dana Farber Cancer Institute, discusses how treatment for patients with acute myeloid leukemia has evolved in recent years. 

Ilene Galinsky Highlights Evolution of AML Treatment

At a 2-year follow-up, lisocabtagene maraleucel (liso-cel; Breyanzi) continued to yield positive outcomes in patients with relapsed/refractory large B-cell lymphomas (LBCL), according to results from the phase 1 TRANSCEND NHL 001 trial (NCT02631044) presented during the 2022 Transplantation & Cellular Therapy Meetings.

Treatment with liso-cel elicited an overall response rate (ORR) of 73% (95% CI, 66.9%-78.1%), including a complete response (CR) rate of 53% (95% CI, 46.6%-59.2%) among 257 efficacy-evaluable patients after a median follow-up of 23.0 months. The median duration of response (DOR) by Lugano 2014 criteria was 23.1 months (95% CI, 8.6–not reached [NR]) and the probability of continued response at 2 years was 49.5% (95% CI, 41.4%-57.0%).

Additionally, the median DOR was 26.1 months (95% CI, 23.1–NR) and 23.1 months (95% CI, 5.6-NR) in those who achieved a CR and partial response (PR), respectively.

“This 2-year follow-up analysis of TRANSCEND demonstrated durable response to liso-cel in patients with high-risk aggressive relapsed/refractory LBCLs,” Jeremy Abramson, MD, director of the Jon and Jo Ann Hagler Center for Lymphoma, Massachusetts General Hospital, and an associate professor of medicine at Harvard Medical School said during the presentation. “Liso-cel treatment was associated with a low incidence of severe cytokine release syndrome [CRS] and neurologic events,” Abramson added.

To be eligible for the study, patients needed to be 18 years or older and have received 2 or more prior lines of therapy. Those who enrolled had diffuse large B-cell lymphoma that was not otherwise specified (DLBCL NOS)—either de novo or transformed from follicular lymphoma, marginal zone lymphoma, or another disease—high-grade B-cell lymphoma (HGBCL), primary mediastinal large B-cell lymphoma (PMLBCL), or follicular lymphoma grade 3B (FL3B). Other inclusion criteria included previous hematopoietic stem cell transplant and an ECOG performance status of 0 or 2. Primary central nervous system lymphoma was also allowed.

Patients received a lymphodepleting regimen of 30 mg/m2 fludarabine and 300 mg/m2 of cyclophosphamide for 3 days followed by liso-cel 2 to 7 days later. The on-study follow up was 24 months.

The study’s primary end points were adverse effects (AE) and ORR by independent review committee (IRC). Secondary end points included CR rate by IRC, DOR, progression-free survival (PFS), overall survival (OS), and pharmacokinetic profile.

Patients who enrolled on the trial were followed for 2 years after the last liso-cel dose, and the study is ongoing as of the cutoff date of January 2021. Two hundred and sixty-eight patients had died or withdrawn 24 months or more after follow-up. Among 120 patients who completed the study, 81 agreed to be part of a long-term follow-up study assessing safety and OS up to 15 years, but no IRC response assessments were performed.

Notably, 1 patient died following an ongoing CR at 26 weeks due to sepsis. No patients relapsed after 23 months in the study.

The median patient age was 63 years and 41% of patients were aged 65 years or older. The majority of patients had DLBCL NOS (51%), and others had transformed follicular lymphoma (22%), other indolent lymphomas (7%), HGBCL (13%), PMBCL (6%), and FL3B (1%). Additionally, most patients were chemotherapy refractory (67%) and underwent treatment with a bridging therapy (59%). The overall median follow up was 19.9 months.

Additional findings from the study indicated that after a median follow-up of 23.9 months, the median PFS was 6.8 months (95% CI, 3.3-12.7) and the probability of PFS at 2 years was 40.6% (95% CI, 34.0%-47.2%). The median PFS in those who had a CR and PR was 27.3 months (95% CI, 24.0-NR) and 6.8 months (95% CI, 3.3-12.7).

After a median follow-up of 29.3 months, the median OS was 27.3 months (95% CI, 16.2-45.6), with a 2-year probability of OS rate of 50.5% (95% CI, 44.1%-56.5%). The median OS in those who had a CR or PR was 48.5 months (95% CI, 45.2-NR) and 9.0 months (95% CI, 6.0-11.4), respectively. In non-responders, the median OS was 5.4 months (95% CI, 2.9-6.5). Three deaths occurred after 45 months. Moreover, CAR T-cell persistence was detected at 48 months in the long-term follow-up study (NCT03435796) in addition to 37% of patients at 24 months in the TRANSCEND study.

In terms of safety, the most common any AEs within 90 days of infusion were neutropenia (63%), anemia (48%), and fatigue (44%), and grade 3 or higher AEs include neutropenia (60%), anemia (37%), and thrombocytopenia (27%). Any grade and grade 3 or higher infections occurred in 12% of patients, and in 41% of patients with any grade AE. From day 91 to the end of study, the most common any grade AEs were neutropenia (8%), anemia (8%), and fatigue (7%), with grade 3 or higher AEs including neutropenia (7%), anemia (6%), and thrombocytopenia (4%). Any grade and grade 3 or higher infections occurred in 5% of patients, and in 10% of patients with any grade AE.

Investigators reported several AEs of special interest. Any grade and grade 3/4 CRS were reported in 42% and 2% of patients, respectively; the median time to onset and resolution of CRS was 5 days, respectively. Any grade and grade 3/4 neurologic events were reported in 30% and 10% of patients, respectively. The median time to onset was 9 days and the median time to resolution was 11 days. Most cases of CRS and neurological events were grade 1/2, with no grade 5 events.

Second primary malignancies (SPM) occurred in 5 and 17 patients during the treatment emergent and post–treatment emergent periods, respectively. The types and incidence of SPMs were expected given the patient population and prior therapies and included diseases such as non-melanoma skin cancer (n = 9), solid tumors (n = 4), myelodysplastic syndrome (n = 8), acute myeloid leukemia (n = 2), and peripheral T-cell lymphoma (PTCL; n = 1). The single case of PTCL was reported on day 30 and did not appear to be in relation to treatment with liso-cel.

Of 270 patients, 9 died 30 days or less following last infusion, 24 died at over 30 days to 90 days or less, and 100 died at over 90 days. The majority of deaths were attributed to disease progression and no deaths were due to COVID-19.

Abramson JS, Palomba ML, Gordon LI, et al. Two-year follow-up of TRANSCEND NHL 001, a multicenter phase 1 study of lisocabtagene maraleucel in relapsed or refractory large B-cell lymphomas. Presented at: 2022 Transplantation & Cellular Therapy Meetings; April 23-26, 2022. Abstract 65.

Cheson BD, Fisher RI, Barrington SF, et al. Recommendations for initial evaluation, staging, and response assessment of Hodgkin and non-Hodgkin lymphoma: the Lugano classification. 

. 2014;32(27):3059-3068. doi:10.1200/JCO.2013.54.8800

Patients with relapsed/refractory large B-cell lymphoma continued to derive benefit from lisocabtagene maraleucel after 2 years of follow-up.

Liso-cel Exhibits Durable Responses in Relapsed-Refractory Large B-Cell Lymphoma

Patients with relapsed or refectory large B-cell lymphoma (LBCL) who received axicabtagene ciloleucel (axi-cel; Yescarta) continued to elicit a long-term survival overall survival (OS) benefit at 5-year follow-up, according to data from an analysis of the phase 2 ZUMA-1 trial (NCT02348216) presented during the 2022 Tandem Meeting.

“In this updated 5-year analysis, axi-cel induced long-term OS...among treated patients,” according to Caron A. Jacobson, MD, MMSc, medical director of the Immune Effector Cell Therapy Program and senior physician at Dana-Farber Cancer Institute. “Between the 4- and 5-year analysis, the time to next therapy curve remains stable and 92% of patients remained alive without a need for subsequent therapy, which may be suggestive of a cure in these patients,” said Jacobson, who is also an assistant professor of medicine at Harvard Medical School.

Investigators reported a 5-year OS rate of 42.6% (95% CI, 32.8%-51.9%) following treatment with axi-cel (n = 101). In the population of patients who experienced a complete response, the 5-year OS rate was 64.4% (95% CI, 50.8%-75.1%) and the median OS was not reached (95% CI, 63.4–not estimated). Additionally, 63% of complete responders were alive at the 5-year data cut off. At the 4-year data cutoff, 1 patient died at month 63 and one experienced progressive disease at month 54.

To be considered for treatment, patients were required to have LBCL, including diffuse large B-cell lymphoma, primary mediastinal B-cell lymphoma, or transformed follicular lymphoma. Patients were also required to have not responded to their last chemotherapeutic or have relapsed 12 months or less following autologous stem cell transplant. Treatment with a previous anti-CD20 monoclonal antibody and anthracycline was also necessary.

Those who underwent treatment received a conditioning regimen of cyclophosphamide at 500 mg/m

 of fludarabine for 3 days. This was followed by axi-cel at a dose of 2x106 CAR T-cells/kg. The primary end point was overall response rate with first response assessment 4 weeks following infusion, Key secondary end points included OS, safety, and translational evaluations.

A total of 111 patients were enrolled on the study, 8 of whom did not undergo treatment due to adverse effects (AEs; n = 4), no measurable disease (n = 2), death due to disease progression (n = 1), and manufacturing failure (n =1); this left 103 patients to undergo conditioning. Of these patients 2 were not treated due to AEs and death, respectively. One hundred and three patients underwent infusion. The data cutoff was August 11, 2021 and the median follow-up was 63.1 months.

Additional findings from the trial highlighted a median time to next anticancer therapy of 8.7 months following infusion. A total of 34% of patients were alive at cutoff with no subsequent therapy or retreatment with axi-cel. Two patients who had prior progression underwent new anticancer therapy.

According to results of an exploratory analysis, investigators reported that 1- and 2-year event-free survival (EFS) may potentially have a role as a surrogate end point for long-term OS. The 5-year OS rates among those who had or had not experienced an EFS event at month 12 were 5.3% vs 90.9%, respectively. The median OS was 8.3 months among those who experienced an event and was not reached in those who did not experience an event. Additionally, the 5-year OS rates among those who did or did not have an EFS event at month 24 were 11.3% and 92.3%, respectively. Moreover, the median OS in both respective groups was 9.2 months and not reached.

Investigators also determined that early CAR T-cell expansion was associated with ongoing response at 60 months. The median peak CAR T levels appeared to be numerically higher in those who had an ongoing response at month 60 and lower in those who relapsed or did not respond to treatment. Similarly, another trend was observed in those who experienced CAR T-cell expansion by area under the curve from day 0 to 28.

A total of 58% of patients had died by the cutoff date. No new safety signals had been observed as of the 5-year data cutoff, including serious AEs or secondary malignancies related to treatment. Patients most commonly died due to progressive disease (n = 45), AEs (n = 4), secondary malignancies (n = 1), or other reasons (n = 9).

Jacobson C, Locke FL, Ghobadi A, et al. Long-term (5 year) overall survival in Zuma-1, the pivotal study of axicabtagene ciloleucel (Axi-Cel) in patients with refractory large B-cell lymphoma (LBCL). Presented at: 2022 Tandem Meetins; April 23-26, 2022; Salt Lake City, UT. Abstract 10.

Patients with relapsed or refractory large B-cell lymphoma experienced improved overall survival following treatment with axicabtagene ciloleucel.

 Axi-cel Sustains Long-Term Survival Rates in Relapsed/Refractory Large B-Cell Lymphoma 

Belimumab (Benlysta) may be a useful treatment for the prevention of chronic graft-vs-host-disease (cGVHD) in patients undergoing allogeneic hematopoietic transplantation, although a larger confirmatory trial is still warranted, according to study results presented at the 2022 ASTCT Meeting.

Belimumab, which is FDA approved for adults with systematic lupus erythematosus and active lupus nephritis, was found to be very well tolerated and also was not linked to any severe infections or myelosuppression when administered to patients in remission from hematologic malignancies.

Overall, 2 out of the 9 patients who received belimumab on study developed moderate to severe cGVHD. One patient died and the other did have an initial response to therapy.

“These data describe, for the first time, [the] use of belimumab for chronic GVHD prophylaxis,” Iskra Pusic, MD, MSCI, of the Division of Oncology at Washington University School of Medicine in St. Louis, noted in a presentation of the findings. “Belimumab was very well tolerated, and the absence of severe infections and myelosuppression is very reassuring.”

Belimumab is a human monoclonal antibody that functions by preventing B-cell activating factor (BAFF) from binding to its receptors on B cells, thus preventing aforeactive B cells from surviving. Because B cells play an important role in cGVHD pathophysiology and because BAFF plays a substantiated role in cGVHD by promoting BCR signaling, investigators hypothesized that belimumab could be effective at prevention of this disease.

“The coordinated interaction and response between T cells and B cells are required for further perpetuation of chronic GVHD,” Pusic explained. “We know that selective modulation of this alloreactive response rather than general immunosuppression would be a promising mechanism for prevention of GVHD, while still allowing and preserving [the] graft-vs-leukemia effect.”

To that end, this single-center, investigator-initiated phase 1 trial enrolled 9 patients with acute myeloid leukemia (AML), acute lymphocytic leukemia (ALL), myelodysplastic syndromes (MDS), and lymphoma to evaluate whether targeting BAFF early after allogenic hematopoietic transplant would have a favorable effect on the incidence or severity of cGVHD.

Enrolled patients were adults in complete remission and tested negative for minimal residual disease 30 days after transplant. Patients had received mobilized peripheral blood stem cells from 10/10 haploidentical-matched related or unrelated donors. Cells received either myeloablative or non-myeloablative conditioning, and tacrolimus, methotrexate, and antithymocyte globulin were allowed. Seven out of the 8 patients were treated with ATG and 1 was treated with posttransplant cyclophosphamide.

Patients received belimumab at 10 mg/kg every 2 weeks for 3 doses followed by 4 more doses at monthly intervals. Treatment initiation began 50 to 80 days following allogeneic hematopoietic cell transplantation.

Patients who received at least 1 dose were evaluable for safety, and patients who received at least 2 doses were evaluable for both safety and efficacy.

The median follow-up time after transplant was 28 months (range, 12-43); the median time since belimumab completion was 23 months (range, 4-29).

Eight of 9 patients successfully received all 7 of the preplanned doses of belimumab. After more than 20 months of follow-up (range, 20-29 months), 5 are alive with no evidence of cGVHD.

Two patients developed cGVHD of the skin, eye, mouth, and liver. For 1 patient, this occurred following their fifth cycle of belimumab; however, their condition improved through treatment with tacrolimus, ruxolitinib (Jakafi), and steroids administered via a tapered schedule. Unfortunately, the other patient died from pneumonia complications after cGVHD occurred 2 months beyond their last belimumab cycle.

Another patient completed all 7 cycles but relapsed with AML 1 month later and was treated with enasidenib (Idhifa) and donor lymphocyte infusion. This patient is now 16 months posttreatment and receiving prednisone for mild oral and upper gastrointestinal cGVHD.

One patient experienced thrombocytopenia and consequently had to reduce their dose to 3 cycles—3 months later, this patient relapsed with lymphoma. Three patients developed stage 1 skin acute GVHD; 2 cases resolved completely with a steroid pulse, and 1 case developed into overlap cGVHD.

No adverse events equal to or greater than grade 3 were reported. There were also no signification infections or myelosuppression, although 1 patient had cytomegalovirus reaction. No patients demonstrated any infusion reactions or hypersensitivity.

“While the result of our study really needs further validation in a larger trial to further assess the impact of belimumab on incidences of chronic GVHD, these preliminary results are encouraging,” Pusic said.

Furthermore, risk stratification should be an important consideration in future studies, she concluded, noting that correlative studies have been launched because B-cell reconstitution was delayed.

Pusic I, Johanns T, Sarantopoulos S, et al. Use of belimumab for prophylaxis of chronic graft-versus-host disease. Presented at: 2022 Tandem Meetings Transplantation & Cellular Therapy Meetings of ACTCT and CIBMTR; April 23-26, 2022; Salt Lake City, UT. Abstract 34.

Belimumab has emerged as a safe and tolerable agent that may be useful for the prophylaxis of chronic graft-vs-host-disease.

Belimumab May Help Prevent Chronic GVHD in Adults Undergoing Allogenic Transplant

Patients with myelofibrosis who have moderate or severe thrombocytopenia experienced physical function–related symptoms including tiredness and inactivity, according to a retrospective analysis of the phase 3 PERSIST-2 study (NCT02055781) presented at the National Comprehensive Cancer Network (NCCN) 2022 Annual Conference. However, pacritinib, which has been recently approved by the FDA, seeks to fill an unmet symptom burden need for this patient population, according to investigators.

“Tiredness and inactivity represent the most prevalent burden for patients with myelofibrosis with moderate to severe thrombocytopenia,” Ruben A. Mesa, MD, director of The University of Texas Health San Antonio MD Anderson Cancer Center, said.

Data from the analysis showed that tiredness was the most severe symptom in the overall population (N = 259) with a median symptom severity score of 6. Patients with moderate or severe baseline thrombocytopenia were included and stratified by baseline platelet count; 50-100 × 10

/L (n = 118) vs less than 50 × 109/L (n = 141).

Patients with severe thrombocytopenia had a higher combined median score of tiredness plus inactivity compared with patients with moderate thrombocytopenia, 12 vs 10, respectively (

Investigators of the PERSIST-2 study (NCT02055781) evaluated the safety and efficacy of the oral JAK2 inhibitor pacritinib (Vonjo) in adult patients with primary or secondary myelofibrosis. To be eligible for the trial, patients needed to have a platelet count of 100 × 10

/L or less. Prior treatment with a JAK2 inhibitor was permitted.

The trial randomized a total of 311 patients 1:1:1 to receive pacritinib 400 mg once daily, pacritinib 200 mg twice daily, or best available therapy. The coprimary end points of the trial were spleen volume response of at least a 35% at week 24 and at least a 50% total symptom score (TSS) reduction at week 24.

On February 28, 2022, the FDA granted pacritinib an accelerated approval for the treatment of adults with intermediate or high-risk primary or myelofibrosis with a platelet count below 50 × 10

/L. The approval was based on results from PERSIST-2.

In the analysis presented at the NCCN 2022 Annual Conference, symptom scores were evaluated using TSS 2.0 and were averaged for the week prior to randomization. Symptom prevalence was defined by a symptom score of at least 1 on a scale of 1 to 10.

Patients in the moderate group had a median age of 69 years (range, 64-74) compared with 67 years (range, 62-74) in the severe group. The median platelet count in moderate group was 28 × 109/L (range, 18 × 10

/L) among patients with a higher platelet count. Median hemoglobin was comparable in both arms, 9.2 g /dL (range 8.2 g/dL to 10.6 g/dL) and 9.4 g/dL (range, 8.4 g/dL to 11.0 g/dL) in the lower and higher platelet count arms, respectively. Patients with peripheral blasts of at least 1% were more common in the moderate cohort (48.2%) compared with the severe group (40.7%).

Patients with moderate thrombocytopenia had a mean TSS score of 22 and the average TSS score in this group was 23.7 (range, 4.0-58.4). Similarly, patients with severe thrombocytopenia had a median TSS score of 23 and the average TSS score was 25.7 (range, 3.0-64.3).

Additional results from the analysis showed that inactivity had a symptom severity score of approximately 5.5 and approximately 4.5 among patients in the moderate and severe cohorts, respectively. In terms of spleen-related symptom severity, patients with moderate thrombocytopenia had median symptom severity scores of approximately 5 for early satiety, approximately 3 for abdominal discomfort, and 2.5 for left rib pain. For patients with severe thrombocytopenia, these scores were approximately 5, approximately 4, and approximately 2, respectively.

Patients with moderate disease also had higher median symptom severity scores compared with those with severe disease for the cytokine-related symptoms of night sweats (approximately 3 vs approximately 2.5, respectively) and bone pain (approximately 2 vs approximately 1.5, respectively).

All symptoms examined in the analysis had a prevalence of at least 50% at both platelet levels. Common symptoms in the moderate group included tiredness (approximately 95%), inactivity (approximately 90%), early satiety (approximately 90%), abdominal discomfort (approximately 80%), and night sweats (approximately 70%). Among patients with severe thrombocytopenia common symptoms were made up of tiredness (approximately 95%), inactivity (approximately 85%), early satiety (approximately 85%), abdominal discomfort (approximately 75%), and night sweats (approximately 70%).

“As pivotal phase 2 studies for the JAK1/2 inhibitors ruxolitinib [Jakafi] and fedratinib [Inrebic] excluded patients based on lower platelet counts less than 50,000/µL or 100,000/µL, respectively, an unmet need remains for therapies that can improve symptomatic disease with myelofibrosis and limits [the effect] to their platelet count; pacritinib may fill this role,” Mesa said. “These data are even more relevant in light of the recent approval of pacritinib for patients with a platlet count of less than 50,000/µL.”

Specifically, pacritinib showed a marked spleen volume reduction of at least 35% compared with BAT. Among Investigators individuals with a platelet count of less than 50 × 10

/L, those who received pacritinib at the recommended 200-mg twice-daily dose (n = 31), 29.0% (95% CI, 14.2%-48.0%) had a reduction in symptom burden vs 3.1% (95% CI, 0.1%-16.2%) of those who received BAT (n = 32).

In terms of TSS, 26% of patients who received pacritinib had a reduction of at least 50% using the Modified Myelofibrosis Symptom Assessment Form compared with 9% of those who received BAT.

Mesa R, Palmer J, Bose P, et al. Symptom burden in patients with myelofibrosis who have moderate or severe thrombocytopenia: a retrospective analysis of patients enrolled in the PERSIST-2 study. 

. 2022;20(3.5):CLO22-067. doi:10.6004/jnccn.2021.7287

CTI BioPharma announces FDA accelerated approval of Vonjo (pacritinib) for the treatment of adult patients with myelofibrosis and thrombocytopenia. News release. CTI BioPharma. February 28, 2022. Accessed April 14, 2022. 

Vonjo. Prescribing information. CTI BioPharma Corp; 2022. Accessed April 15, 2022. bit.ly/3tO1bqm

Pacritinib helps relieve physical function-related symptoms in adult patients with myelofibrosis and moderate or severe thrombocytopenia.

Newly Approved Pacritinib Continues to Reduce Symptom Burden in Myelofibrosis With Moderate/Severe Thrombocytopenia

Bone marrow transplantation (BMT) is a common treatment for advanced hematologic malignancies. During the process, the patient’s hematologic system is eradicated using chemotherapy and radiation therapy. The type of transplant a patient receives is dependent on their diagnosis and/or comorbidities.

An autologous transplant will require mobilization of stem cells. This is achieved by administration of chemotherapy and/or growth factors. Recovery is usually quicker with less complications. Allogeneic transplant is replaced with healthy hematopoietic cells from a human leukocyte antigen–matched donor to constitute a new blood-forming system. The lengthy process can be grueling, and BMT recipients typically become immunocompromised. As a result of myelosuppression, patients are at increased risk of neutropenia.

Special protocols are required to minimize the patient’s risk of infection and to treat or prevent adverse effects. Oncology nurses typically provide prophylactic anti-infection measures and educate patients and caregivers about the protocols they must follow. These measures may include the following:

Antimicrobials such as ciprofloxacin (CiproXR), penicillin v potassium, and trimethoprim-sulfamethoxazole (Bactrim) given prophylactically

Antivirals such as acyclovir (Sitavig, Zovirax), valacyclovir (Valtrex), and ganciclovir (Zirgan) to prevent herpes simplex virus and cytomegalovirus infections

Antifungals, including fluconazole (Diflucan), voriconazole (Vfend, Vfend IV), and posaconazole (Noxafil)

Antiemetics to prevent or treat nausea and vomiting

Electrolyte supplements to maintain normal potassium, magnesium, calcium, and phosphorus levels

Granulocyte colony-stimulating factor is given to shorten the time to engraftment

Transfusions of red blood cells and platelets in the early posttransplant period to treat thrombocytopenia and anemia until the bone marrow graft begins to produce new blood cells

Inflammation or excoriation of the oral mucosa and the gastrointestinal tract because of pretransplant chemotherapy or radiation therapy manifests as stomatitis and dysphagia, which can reduce quality of life, prolong the hospital stay, and raise infection risk. Antioral mucositis measures include the following:

Cryotherapy (ice chips or ice pops) before, during, and after melphalan administration for a total of 2 hours to induce vasoconstriction and slow melphalan absorption

Calcium phosphate (Caphosol) mouth rinse and Magic Mouthwash (diphenhydramine [Benedryl], aluminum hydrozide/magnesium hydroxide/simethicone [Mylanta], and lidocaine viscous) to soothe the oral mucosa

Preventive treatment should start before chemotherapy or radiation treatment and continue as needed.

Use antiemetics as needed and replete fluids and electrolytes. Patients may benefit from eating smaller meals more frequently, avoiding fatty foods, eating drier foods with fluids in between, and consuming saltier foods, such as crackers and pretzels.

. Use antidiarrheal medications and replete fluids/electrolytes as needed. High-fiber foods, nuts, seeds, fatty or fried foods, spicy foods, caffeinated beverages, foods containing sorbitol or lactose, and sugar substitutes should be limited. Daily fluid intake should be 8 to 10 cups.

Patients should consult with a registered dietitian before, during, and after transplant as needed.

Maintaining good oral hygiene helps improve the taste of foods. Patients may enjoy tart foods, such as lemon, yogurt, and pineapple.

Prevention and Treatment of Complications

 occurs when donor cells recognize the recipient’s tissues as foreign and mount an attack, which can be life-threatening. GVHD most commonly causes irritation of the skin, liver, gastrointestinal tract, and lungs. Acute GVHD occurs from a few days after transplant up to day 90 posttransplantation. Chronic GVHD persists from day 90 and beyond. Immunosuppressant medications, such as steroids, methotrexate (Trexall), cyclosporine (Sandimmune, Neoral, Gengraf), and tacrolimus (Prograf), are given to reduce GVHD severity.

primarily affects allogeneic transplant recipients with preexisting liver disease and GVHD. Small blood vessels in the liver become injured and occluded, causing ascites, weight gain, and jaundice. This life-threatening condition is commonly seen in the patients who receive melphalan, cyclophosphamide, and busulfan during pretransplant conditioning. Early diagnosis of VOD decreases morbidity and mortality rates.

is lung inflammation, occurring as early as the first 100 days posttransplant. Late-onset pneumonitis can arise up to 2 years posttransplant. Pneumonitis can be induced by GVHD, chemotherapy, or radiation. Early diagnosis and treatment are essential.

A psychosocial assessment should be performed before and after transplant to address each patient’s ongoing emotional and practical needs. Examples include caregiver support, financial concerns, medication adherence, child care, sexuality, housing, and transportation.

Absolute neutrophil count of at least 500 to 1,000 mm

Plate count of at least 15,000 to 20,000 mm

Nausea, vomiting, and diarrhea are controlled

Able to swallow medications and keep them down for 48 hours

Caregiver at home in a safe and supportive environment

Education of patients and their caregivers is a vital role of the oncology nurse on the BMT service to help transplant recipients optimize their health. To reduce the risk of infection and complications, patients should practice the following:

Take temperature twice daily and record it

Use a soft toothbrush and nonwhitening toothpaste

Avoid flossing if the patient did not regularly floss before transplant

Follow a low-microbial diet (no aged cheeses and unpasteurized foods, all foods well cooked)

No driving immediately after transplant, and patients should ride in the back seat if platelet count is less than 50,000

Avoid close contact with people with respiratory illness symptoms

Avoid direct contact with soil and plants, which increases exposure to potential pathogens

Avoid cleaning cat litter and scooping dog feces

Advise patients to contact their physician if they experience any of the following:

Fever of 100.4o F or more, even if they feel well

Shortness of breath or changes in breathing

Uncontrolled nausea, vomiting, or diarrhea

Stem cell or bone marrow transplant. American Cancer Society. Accessed February 23, 2022. https://bit.ly/36C9cqn

Preventing infection after bone and marrow transplant. Cleveland Clinic. Updated August 8, 2019. Accessed February 23, 2022. 

Hesketh PJ, Kris MG, Basch E, et al. Antiemetics: ASCO Guideline Update. 

. 2020;(38)24:2782-2797. doi:10.1200/JCO 20.01296

Cryotherapy against oral mucositis after high-dose melphalan. ClinicalTrials.gov. Updated October 15, 2018. Accessed February 23, 2022. https://bit.ly/3pcgmrH

Younus J, Kligman L, Jawaid MA, Dhalla A. Treatment of active mucositis with caphosol (calcium phosphate): a retrospective case-series. 

. 2013;4(3):147-150. doi:10.4021/wjon683e

Special protocols are required to ensure the safety of patients undergoing bone marrow transplants.

Hematology