In the frontline setting of chronic graft-vs-host disease (cGVHD), ibrutinib (Imbruvica) plus prednisone did not elicit better response rates than placebo plus prednisone, thus missing the primary end point of the phase 3 iNTEGRATE trial (NCT02959944), according to primary and final analyses of the study that were published in the 

Patients treated with the combination (n = 95) experienced a 48-week response rate of 41% compared with 37% in the placebo plus prednisone arm (n = 98; 

= .54). Among the responders, 9% (n = 9) and 6% (n = 6) of patients in the ibrutinib and placebo arms, respectively, achieved a complete response (CR).

“The iNTEGRATE study represents the first phase 3 therapeutics trial in previously untreated cGVHD using objective response criteria,” lead study author David Bernard Miklos, MD, PhD, of Stanford University School of Medicine in California, said. “This was a negative study, yet positive trends in other cGVHD end points like withdrawal of immunosuppression and patient-reported outcomes concern me.”

Patients ages 12 years and older were eligible for this trial if they had newly diagnosed, previously untreated moderate or severe cGVHD requiring systemic corticosteroid therapy. Patients were excluded if they had received prior systemic treatment for cGVHD, however, patients who had received other prophylaxis immunosuppressants or treatment for acute graft-vs-host disease were eligible.

A total of 193 patients were randomized 1:1 to receive ibrutinib 420 mg once daily plus prednisone starting at 1 mg/kg once daily or placebo plus prednisone. Ibrutinib or placebo was given until cGVHD progression, initiation of another systemic cGVHD treatment, relapse of an underlying malignancy, or unacceptable toxicity.

Patients received prednisone until unacceptable toxicity. Prednisone could also be tapered using a 6-month taper schedule. Patients in the ibrutinib arm received a mean of 4.9 g of prednisone while in the study (median, 4.2 g; range, 0-18), and patients in the placebo arm received a mean of 5.4 g of prednisone (median, 4.1 g; range, 0-22). Patients received a median total dose of 4 g of prednisone in both arms.

The primary end point of iNTEGRATE was 48-week response rate, defined as CR or partial response (PR) in at least 1 organ or site without progression in any other organ or site. Secondary end points included event-free survival (EFS), failure-free survival (FFS), duration of response (DOR), time to withdrawal of immunosuppressants including and excluding ibrutinib, time to corticosteroids withdrawal, Lee cGVHD Symptom Scale score improvement, overall survival (OS), and safety.

At data cutoff, the median treatment duration in the ibrutinib arm was 5 months (range, 0-44) for ibrutinib and 5 months (range, 0-34) for prednisone. The median treatment duration in the placebo arm was 6 months (range, 0-36) for placebo and 6 months (range, 0-44) for prednisone. The median relative ibrutinib dose intensity was 100%.

At a median follow-up of 33 months (range, 0.03-47.20), all patients had discontinued ibrutinib or placebo. The most common reasons for treatment discontinuation were progressive cGVHD (ibrutinib, 23%; placebo, 31%), adverse effects (AEs) unrelated to cGVHD (ibrutinib, 20%; placebo, 16%), and investigator decision (ibrutinib, 23%; placebo, 27%). In addition, 8% of patients (n = 15) discontinued ibrutinib (n = 13) or placebo (n = 2) because of study closure, and 3% of patients on ibrutinib (n = 3) discontinued study ibrutinib and continued with other ibrutinib treatment as part of a long-term access study.

At 48 weeks, 4% (n = 4) and 2% (n = 2) of patients had stable disease, 24% (n = 23) and 35% (n = 34) had progressive disease, and 1% (n = 1) and 3% (n = 3) had a cGVHD flare in the ibrutinib and placebo arms, respectively.

At an additional 96-week follow-up, ibrutinib plus prednisone demonstrated a response rate of 27% compared with 22% with placebo plus prednisone (

= .43). At this follow-up, 14% (n = 13) and 9% (n = 9) of patients had a CR in the ibrutinib and placebo arms, respectively. Treatment with ibrutinib plus prednisone resulted in a reduced best overall response in the liver and lower gastrointestinal tract.

In patients who had a CR or PR at any time during the study, the median DOR was 19.09 months (95% CI, 7-not evaluable) in the ibrutinib arm and 10.22 months (95% CI, 6.5-17) in the placebo arm (HR, 0.717; 95% CI, 0.482-1.068; 

= .10). The 24-month DOR estimates were 45% (95% CI, 33%-56%) and 32% (95% CI, 22%-42%) in the ibrutinib and placebo arms, respectively.

The median EFS was 14.98 months (95% CI, 6-27) in the ibrutinib arm and 8.31 months (95% CI, 6-13) in the placebo arm (HR, 0.756; 95% CI, 0.535-1.066; 

= .11). The earliest events for each patient included cGVHD progression (ibrutinib, 27%; placebo, 44%), initiation of subsequent cGVHD treatment (ibrutinib, 19%; placebo, 21%), death (ibrutinib, 11%; placebo, 1%), and underlying malignancy relapse (ibrutinib, 5%; placebo, 8%). The 24-month EFS estimates were 43% (95% CI, 32%-53%) and 28% (95% CI, 19%-37%) in the ibrutinib and placebo arms, respectively.

The median FFS was 16.43 months (95% CI, 8-29) in the ibrutinib arm and 9.10 months (95% CI, 7-18) in the placebo arm (HR, 0.806; 95% CI, 0.566-1.149). The 12-month FFS estimates for the ibrutinib and placebo arms were 56% (95% CI, 45%-66%) and 47% (95% CI, 37%-57%), respectively. The 24-month FFS estimates were 45% (95% CI, 35%-55%) and 33% (95% CI, 23%-42%) in the ibrutinib and placebo arms, respectively.

The median OS was not reached in either arm (HR, 1.061; 95% CI, 0.591-1.904). The 24-month OS estimates were 80% in both arms. At the time of final analysis, 24% (n = 23) of patients in the ibrutinib arm and 22% (n = 22) of patients in the placebo arm had died.

The proportion of patients with at least a 7-point Lee cGVHD Symptom Scale score improvement on at least 2 consecutive visits was 43% (n = 41) and 31% (n = 30) in the ibrutinib and placebo arms, respectively (

Corticosteroid withdrawal occurred in 47% and 39% of patients in the ibrutinib and placebo arms, respectively (

= .28). Additionally, at 24 weeks, 41% and 46% of patients in the ibrutinib and placebo arms, respectively, had received a reduced prednisone dose of less than 0.15 mg/kg/d for at least 30 days.

A total of 39% and 31% of patients in the ibrutinib and placebo arms, respectively, withdrew from all immunosuppressants, excluding ibrutinib or placebo (

= .22). In total, 18% (n = 17) and 8% (n = 8) of patients withdrew from all immunosuppressants, including ibrutinib and placebo, in the ibrutinib and placebo arms, respectively (

= .03). The 24-month cumulative incidence rates of immunosuppressant withdrawal, including ibrutinib, were 0.17% (95% CI, 0.10%-0.26%) and 0.08% (95% CI, 0.03%-0.14%) in the ibrutinib and placebo arms, respectively.

In the safety population, which included all patients who received at least 1 dose of study drug, 99% of patients in each arm experienced any-grade treatment-emergent AEs (TEAEs; ibrutinib, n = 93/94; placebo, n = 95/96). The most common any-grade TEAEs in the ibrutinib and placebo arms, respectively, were insomnia (28% vs 19%), peripheral edema (27% vs 15%), and cough (21% vs 30%). The most common grade 3 or higher TEAEs of clinical interest in the ibrutinib and placebo arms, respectively, were opportunistic infections (6% vs 2%), hyperglycemia (4% vs 7%), hypertension (5% vs 5%), major hemorrhage (3% vs 4%), atrial fibrillation (2% vs 2%), and cardiac arrest (1% vs 1%).

In total, 52% (n = 49) and 49% (n = 47) of patients in the ibrutinib and placebo arms, respectively, experienced serious AEs of any grade, and 28% (n = 26) and 27% (n = 26) of patients in the ibrutinib and placebo arms, respectively, experienced serious corticosteroid-related AEs. A total of 49% and 47% of patients in the ibrutinib and placebo arms, respectively, experienced grade 3 or higher serious AEs.

AEs leading to dose reduction occurred in 10% (n = 9) of patients in the ibrutinib arm and 11% (n = 11) of patients in the placebo arm. Additionally, 23% (n = 22) and 28% (n = 27) of patients experienced AEs leading to study drug discontinuation in the ibrutinib and placebo arms, respectively. A total of 13% (n = 12) and 6% (n = 6) of patients in the ibrutinib and placebo arms, respectively, experienced fatal AEs.

“This trial proved that it is feasible to conduct multi-institutional trials using the National Institutes of Health [NIH] consensus criteria for cGVHD, a disease that has many different presentations and in which severity and response to therapy isn’t easy to objectively measure. There are many lessons to be learned and used in the design of future trials and further refinements of NIH consensus criteria,” study author Mohammad Abu Zaid, MD, of the Melvin and Bren Simon Cancer Center at Indiana University in Indianapolis, concluded.

Miklos DB, Abu Zaid M, Cooney JP, et al. Ibrutinib for first-line treatment of chronic graft-versus-host disease: results from the randomized phase III iNTEGRATE study. 

Published online January 6, 2023. doi:10.1200/JCO.22.00509

Articles

First-line ibrutinib plus prednisone missed the primary endpoint in the phase 3 iNTEGRATE trial by not improving the response rate in patients with chronic graft-versus-host-disease compared with placebo plus prednisone. 

Ibrutinib Plus Prednisone Does Not Improve Response Rates in cGVHD 

Lindsay Fischer is an editor at ONN. She joined MJH life sciences in 2021 after graduating from Rutgers University with majors in both English and Spanish and a minor in creative writing. When she is not writing, or researching the latest oncology nursing news, Lindsay is an amateur backpacker and rollerblader. Email Lindsay at lfischer@mjhlifesciences.com

Idecabtagene vicleucel (ide-cel; Abecma) demonstrated an efficacy and safety profile in real-world patients with relapsed or refractory multiple myeloma (RRMM) that was comparable to what was observed in the phase 2 KarMMa trial (NCT03601078), even though 75% of patients would not have met the trial eligibility criteria. Findings were published in a retrospective analysis in the 

Out of 196 patients, 159 received ide-cel by the time of data cutoff. In this group, the rate of any-grade or grade 3 or higher cytokine release syndrome (CRS) was 82% (n = 131), and 3% (n = 5), respectively. Any-grade neurotoxicity was observed in 18% of patients (n = 29) and grade 3 or higher events were reported among 6% (n = 9).

The rate of best overall response was 84% with a complete response (CR) or better rate of 42%. Moreover, at a median follow-up of 6.1 months from infusion, the median progression-free survival (PFS) was 8.5 months (95% CI, 6.5-not reached [NR]), and the median overall survival was 12.5 months (95% CI, 11.3-NR).

Of note, a multivariable analysis identified that the following baseline characteristics were linked with inferior PFS: previous B-cell maturation antigen-targeted therapy use (BCMA-TT; HR, 2.81; 95% CI, 1.44-5.51; 

 = .003), high-risk cytogenetics (HR, 2.31; 95% CI, 1.34-3.97; 

 = .003), an ECOG performance status of 2 to 4 at time of lymphodepletion (HR, 0.97; 95% CI, 0.95-1.00; 

 = .043), and younger age (HR, 2.19; 95% CI, 1.16-4.14; 

“Overall, we observed comparable efficacy and toxicity with ide-cel as reported in the KarMMa trial although 75% of our patients would not have met KarMMa eligibility criteria,” wrote Doris K. Hansen, MD, of the Department of Blood Marrow Transplant and Cellular Immunotherapy at Moffitt Cancer Center, and co-investigators, in the study. “The most common reasons for trial ineligibility included inadequate organ function, prior exposure to BCMA-TT, cytopenias, and poor performance status.”

Further, they noted that 90% of eligible patients were administered ide-cel in the real-world setting, which is comparable with the 91% administration rate in the KarMMa trial.

“Our data indicate that CAR T administration in the real world is feasible, safe, and effective, even among patients with comorbidities,” study authors said.

 for patients with RRMM, after 4 or more prior lines of therapy, including an immunomodulatory agent, a proteasome inhibitor, and an anti-CD38 monoclonal antibody.

In KarMMa, the overall response rate (ORR), CR rate and minimal residual disease (MRD) negative rates were 73%, 33%, and 26%, respectively.

 However, the KarMMa trial eligibility criteria are not believed to best represent patients for whom ide-cel is a standard of care, particularly because most patients with comorbidities would not have been able to participate in the trial.

 The goal of this retrospective analysis, therefore, was to see how the profile of ide-cel translated to a population of real-world patients.

Investigators assessed data retrospectively collected from patients with RRMM who underwent leukapheresis across 11 different institutions in order to receive commercial ide-cel. The American Society of Transplantation and Cellular Therapy guidelines were used to both grade and manage corresponding toxicities, according to each institution’s policies. Patient responses were graded in accordance with the International Myeloma Working Group response criteria.

All patients included in this analysis had received at least 4 prior lines of therapy and underwent leukapheresis between April 1, 2021, and February 28, 2022. Following leukapheresis, patients could receive bridging therapy in the form of chemotherapy and/or radiation at the discretion of the treating physician. Lymphodepleting chemotherapy was administered once daily on days –5, –4-, and –3 leading up to CAR T-cell infusion.

A total of 196 patients completed leukapheresis with intent to manufacture and receive commercial ide-cel. At data cutoff, 17 patients were unable to receive CAR T, 5 because of manufacturing failure and 12 because of a disease progression or death. Twenty patients were pending infusion.

Study authors noted that a key component of administering CAR T-cell therapy is the successful and timely manufacturing of the product. In the real-world analysis, manufacturing error occurred in 6% (n = 12 of 196) of patients undergoing first apheresis, which was higher than the rate of manufacturing failure seen in the KarMMA trial (n = 1 out of 140). They speculated that poor bone marrow reserves could contribute to this, and they argue that future efforts should consider factors associated with poor CAR T-cell manufacturing to allow for optimal patient selection. Seven of those who had manufacturing failure (58%) were able to successfully repeat apheresis.

The median number of days spent in the hospital was 9 (range, 5-69 days). The percentage of patients who received tocilizumab (Actemra), anakinra, or glucocorticoids for CRS, neurological toxicity, or both was 71%, 5%, and 26%, respectively.

The rates of any-grade neutropenia, anemia, and thrombocytopenia was 97%, 95%, and 95%, respectively. The percentage of patients who experienced these adverse events (AEs) at a grade 3 or worse severity was 88%, 51%, and 68%.

Thirty days postinfusion, there was evidence of neutropenia in 60% of patients, anemia in 38%, and thrombocytopenia in 59%. Moreover, 74% of patients received granulocyte colony-stimulating factor, 15% received a thrombopoietin agonist, and 5% received an autologous stem-cell boost. The rate of infection was 34% (n = 52), this included 31 bacterial (20%), 24 viral (16%), and 2 fungal infections (1%).

At the last follow-up, 19% (n = 31) patients who received commercial ide-cel had died, this included 20 deaths related to disease progression, 8 nonrelapse-related deaths, and 2 deaths for which the cause was unknown. Nonrelapse related mortality causes included grade 5 CRS, hemophagocytic lymph histiocytosis along with concomitant grade 5 CRS, neurological toxicity, COVID-19 disease, and cardiomyopathy.

A total of 159 patients were evaluable at day 30 and best overall responses; 149 patients were evaluable for 90-day responses since 10 patients who were in active follow-up had not reached this time point.

ate of CR or better after commercial ide-cel were 84% and 42%, respectively. In patients who received CR or a stringent complete response, 72% reached MRD-negative status.

The 30-day ORR rate was 78% and the 90-day ORR was 72%; the corresponding CR rates were 30% and 38%, respectively. The median time for both overall response and the rate of CR or better was 30 days. The median duration of response was 8.6 months (95% CI, 6.6-NR).

Limitations of the study include the retrospective design, limited follow-up, and heterogeneity in institutional standard for toxicity management across different centers, according to the investigators.

“The safety profile of ide-cel in our real-world cohort was comparable with those in the KarMMa trial, with similar rates of CRS, [neurotoxicity], infections, and persistent cytopenias,” study authors concluded. “It is feasible to administer ide-cel as [standard of care], with high response rates and low incidence of severe CRS and [neurotoxicity], although persistent cytopenias remain an ongoing issue.”

Hansen DK, Sidana S, Peres LC, et al. Idecabtagene vicleucel for relapsed/refractory multiple myeloma: real-world experience from the myeloma CAR T consortium. 

. Published online January 9, 2023. doi:10.1200/JCO.22.01365

Abecma. Prescribing information. Bristol-Myers Squibb Company; 2022. Accessed February 1, 2023. 

Munshi NC, Anderson LD Jr, Shah N, et al. Idecabtagene vicleucel in relapsed and refractory multiple myeloma. 

. 2021;384(8):705-716. doi:10.1056/NEJMoa2024850

Although most patients in the real-world setting would not have met the clinical trial eligibility criteria, the efficacy and safety outcomes with idecabtagene vicleucel were similar for both sets of patients with multiple myeloma. 

Real-World Data Confirm Ide-cel Safety and Efficacy for Patients With Multiple Myeloma

 takes a look back at our most popular stories. In January 2023, data presented at the 2022 

 continued to grab the attention of oncology nurses. Below, find links to poster presentations highlighting new innovations in tamoxifen-related symptom management, and an exclusive interview highlighting key nursing takeaways of interest from the meeting. Moreover, read up on the FDA’s approval of elestrant (Orserdu), which followed updated data presented at the meeting.

Other topics of interest included pain management, a core component of cancer care. However, use of agents to curb these effects, especially opioids, present challenges in practice. Fortunately, the American Society of Clinical Oncology (ASCO) has recently updated their opioid management guideline, providing clearer instruction on best practices with these critical pain management drugs.

Lastly, January is cervical cancer awareness month. 

 published a 4-part weekly series on what oncology nurses need to know to best advocate for their patients with cervical cancer, which included updates in prevention and treatment options.

5. CBD Oil Shows Modest Improvements in Tamoxifen-Related Adverse Effects

 demonstrated that cannabidiol (CBD) oil may be useful in managing tamoxifen-related adverse effect (AEs).

In a study population of 26 patients, the oil was associated with decreases across several AEs related to tamoxifen, including insomnia, hot flashes, arthralgia, mood alterations, and muscle cramps. In addition, median health-related quality-of-life scores increased after 4 weeks with CBD, and the treatment may have demonstrated improvements in endocrine symptoms as well.

Of note, study authors acknowledged that the study period was short and that longer study periods may reveal better insight on whether CBD may provide long-lasting improvements in these domains.

4. Emerging Data Showcases Promising Advancements for Patients With HER2-Low Breast Cancer

 Loyda Braithwaite, MSN, RN, AGPCNP-BC, AOCNP, highlighted promising advances in breast cancer treatments across multiple settings and disease types, including for patients with HER2-low and hormone receptor–positive disease.

In the conversation, Braithwaite, who is an oncology nurse practitioner at the University of Wisconsin Carbone Cancer Center, discussed fam-trastuzumab deruxtecan-nxki’s (Enhertu) performance across the 

 (NCT04553770) trials, as well as sacituzumab govitecan-hziy’s (Trodelvy) expanding use in the hormone receptor–positive setting in TROPiCS-02 (NCT03901339).

She also discussed whether oral SERDs hold the potential to change practice. “[Oral SERDs] are very exciting from the clinician perspective, but also from the patient perspective, to think about the accessibility [options] that we’re going to have to treat them,” she told 

3. ASCO Guidelines Provide Road Map for Cancer Pain Management With Opioids

Unfortunately, 55% of patients experience pain during active treatments, and 66% of patients with advanced disease will experience cancer-related pain. Although guidelines for managing cancer-related pain exist, there are few guidelines focused on exclusively on opioids.

ASCO has updated its guidelines providing recommendations for the management of cancer pain with opioids. A multidisciplinary expert panel consisting of patient representatives and an ASCO guidelines staff member with health research methodology expertise developed the guidelines that were informed by evidence including 16 randomized controlled trials and 31 systemic reviews from January 1, 2010, to February 17, 2022.

The supportive care guidelines addressed 7 key questions for patients with cancer pain under all of which fell under the umbrella of the leading question: “In what circumstances should opioids be used to manage cancer pain in adults, how should opioids be administered, and how should opioid AEs be prevented or managed?”

2. FDA Approves Oral SERD Elacestrant for 

-Mutant ER+, HER2– Metastatic Breast Cancer

On January 27, 2023, the FDA granted an accelerated approval to elacestrant (Orserdu) for the treatment of patients with 

-mutant,estrogen receptor–positive, HER2-negative advanced or metastatic breast cancer following at least 1 prior lines of endocrine therapy. The approval is supported by data from the phase 3 EMERALD study (NCT03778931).

The investigational oral selective estrogen receptor degrader (SERD) was evaluated among patients with 

-mutant disease (n = 115) vs standard-of-care (SOC) endocrine therapy (n = 113) of either fulvestrant or an aromatase inhibitor. The median progression-free survival was 3.8 months (95% CI, 2.2-7.3) vs 1.9 months (95% CI, 1.9-2.1) with the SERD and SOC, respectively (HR, 0.55; 95% CI, 0.39-0.77; 

 = .0005).The overall survival outcomes were not statically significant (HR, 0.90; 95% CI, 0.63-1.30).

Cervical Cancer Prevention Comes Into Focus for Awareness Month

January is cervical cancer awareness month. In this first installment of a weekly series on the oncology nurse’s role in patient advocacy efforts, Debi Fischer, MSW, BSN, BA, LCSW, RN, highlights current educational efforts of disease progression and the Quilt Project.

In 2022, there were 4280 deaths caused by cervical cancer. The FDA has given the greenlight to 3 human papillomavirus (HPV) vaccines: Gardasil, Gardasil 9, and Cervarix. These vaccines are believed to be able to prevent 90% of HPV-attributable cancers. Moreover, Papanicolaou tests is a highly effective screening tool which can help providers combat cervical cancer before it even occurs. If a woman follows screening recommendations, cervical cancer can be found before it becomes invasive and spread. Treatment options are more extensive at this level and in fact precancerous cell changes can also be discovered.

According to Fischer, the advances that have been made in cervical cancer have been significant. Oncology nurses play a significant role about raising awareness, and ensuring that these advances have the opportunity to positively affect their patients.

Each month, Oncology Nursing News® takes a look back at our most popular stories.

Oncology Nursing News Top Stories: January 2023

, Nilesh Kalariya, PhD, AGPCNP-BC, AOCNP; and Laura J. Zitella, MS, RN, ACNP-BC, AOCN, discuss data from the 64th American Society of Hematology Annual Meeting and Exposition that have the greatest potential to change oncology nursing practice.

Kalariya, a nurse practitioner with the Department of Lymphoma/Myeloma at The University of Texas MD Anderson Cancer Center, recently spoke with 

highlighted research from the University of Pennsylvania which showed clinical utility of a frailty phenotype tool and contextualized the role of CAR T-cell therapy for patients with multiple myeloma. He also discussed whether data from a subgroup analysis of patients with multiple myeloma who received the anti-BCMA CAR T-cell therapy in the KarMMa-2 trial (NCT03601078) supports moving it forward in the treatment lineup.

Zitella, a nurse practitioner in the Department of Hematology, Blood & Marrow Transplant, and Cellular Therapies Program at the UCSF Helen Diller Family Comprehensive Cancer Center and an associate clinical professor with the School of Nursing University of California, San Francisco, also spoke with 

, highlighting exciting advances with BTK inhibitors and how nurses can promote safe eating habits after data from ASH demonstrated that the neutropenic diet does not benefit patients. on which data from the 2022 ASH meeting might have the greatest impact on nurses working in hematologic oncology.

Interested in learning more from ASH? Check out our coverage of the 

We want to hear from you! Which ASH data do you think will be practice-changing? Email 

“This study that came out at ASH in a transplant population, which is the most immunocompromised population really highlights the [neutropenic diet] and brings it front and center. Hopefully, this will be enough to convince people to abandon the neutropenic diet.” 

“What we see here is that CAR T-cell therapy, followed by maintenance therapy might be a key in frontline settings to have a longer duration of response.” 

“For relapsed or refractory chronic lymphocytic leukemia, zanubrutinib [Brukinsa] had a better overall response rate and progression-free survival than ibrutinib [Imbruvica].” 

Stephanie Jackson Unpacks Recent Advances in Leukemia Treatments

FDA Grants Pirtobrutinib Accelerated Approval for Relapsed/Refractory MCL

Noncovalent BTK Inhibitors May Fill Unmet Needs in CLL and Other Top ASH Takeaways

Optimizing Frailty Tools Are A Vital Component of Improving Care Across Hematologic Malignancies

Phase 3 Data Support Leaving the “Neutrodiet” Behind After Stem Cell Transplant

Induction and Maintenance With Ibrutinib Proves Effective for Mantle Cell Lymphoma

Zanubrutinib Outperforms Ibrutinib in Head-to-Head Trial for Relapsed/Refractory CLL/SLL

Aaron Gerds on JAK Inhibitor Therapy for Anemic Patients With Myelofibrosis

Gardner A, Mattiuzzi G, Faderl S, et al. Randomized comparison of cooked and noncooked diets in patients undergoing remission induction therapy for acute myeloid leukemia. 

. 2008;26(35):5684-5688. doi:10.1200/JCO.2008.16.4681

Usmani S, Patel K, Hari P, et al. KarMMa-2 cohort 2a: efficacy and safety of idecabtagene vicleucel in clinical high-risk multiple myeloma patients with early relapse after frontline autologous stem cell transplantation. 

. 2022;140(suppl 1):875-877. doi:10.1182/blood-2022-162469

Dhodapkar M, Alsina M, Berdeja J, et al. KarMMa-2 cohort 2c: efficacy and safety of idecabtagene vicleucel in patients with clinical high-risk multiple myeloma due to inadequate response to frontline autologous stem cell transplantation. 

. 2022;140 (suppl 1):7441–7443. doi:10.1182/blood-2022-162615

Stella F, Marasco V, Levati GV, et al. Non-restrictive diet does not increase infections in patients with neutropenia after stem cell transplantation: final analysis of the Neutrodiet multicenter, randomized trial. Presented at ASH 2022. December 10-13, 2022. Abstract 169.

Brown JR, Eichhorst B, Hillmen P, et al. Zanubrutinib or Ibrutinib in Relapsed or Refractory Chronic Lymphocytic Leukemia. 

. Published online December 13, 2022. doi:10.1056/NEJMoa2211582

Mato AR, Woyach, JA, Brown, JR, et al. Efficacy of pirtobrutinib in covalent BTK-Inhibitor pre-treated relapsed / refractory CLL/SLL: additional patients and extended follow-up from the phase 1/2 BRUIN study. 

Dreyling M, Doorduijn, JK,Gine E, et al. Efficacy and safety of ibrutinib combined with standard first-line treatment or as substitute for autologous stem cell transplantation in younger patients with mantle cell lymphoma: results from the randomized triangle trial by the european MCL network. 

Podcasts

Nilesh Kalariya, PhD, AGPCNP-BC, AOCNP; and Laura J. Zitella, MS, RN, ACNP-BC, AOCN, discuss practice-changing presentations from the 64th American Society of Hematology Annual Meeting and Exposition.

ASH Data Offer Treatment Direction for Oncology Nursing Professionals  

Neoadjuvant pembrolizumab (Keytruda) elicited high clinical activity in patients with mismatch repair deficiency (dMMR)/microsatellite instability high (MSI-H) solid tumors and was well tolerated, according to data from a phase 2 study (NCT04082572) published in the 

. Patients who underwent nonoperative management demonstrated promising benefit from the treatment in addition to those who had surgical resection.

The primary end point of the study was pathological complete response (pCR) among those who received 3 doses of pembrolizumab prior to resection. Fifteen patients were evaluable for this end point and had a pCR rate of 67% (95% CI, 38%-88%). At the time of data cutoff, March 31, 2022, 17 patients (49%) underwent surgical resection—including 1 patient after cycle 1, and 1 patient after cycle 2—and achieved a pathological CR rate of 65%. Although the pCR rate of 65% was lower than the study goal of 80%, patients with colorectal cancer (n = 11/14) experienced a pCR rate of 79%.

Among all patients evaluable for radiographic response (n = 33) the overall response rate (ORR) was 82% with a complete response (CR) rate of 30%. Eighteen patients did not undergo surgical resection and either had nonoperative management after 1 year of pembrolizumab (n = 10) or received pembrolizumab for less than a year (n = 8). At median follow-up of approximately 9.5 months (range, 0-26), only 2 patients in the efficacy-evaluable nonoperative arm (n = 17) experienced progression events.

In the cohort of patients who received pembrolizumab for less than a year, 5 patients opted for nonoperative management, 3 patients achieved CRs, 2 experienced stable disease, 1 patient withdrew consent, and 2 patients died from causes unrelated to treatment. Additionally, both patients on the trial with pancreatic cancer (n = 2), experienced adaptive progression and did not achieve a pCR.

“One of the most intriguing findings from this prospective trial is the suggestion that neoadjuvant PD-1–based therapy may represent a definitive approach for dMMR solid tumors enabling organ preservation,” wrote lead study author Kaysia Ludford, MD, of The University of Texas MD Anderson Cancer Center, in Houston, TX, and colleagues, in the paper.

The investigator-initiated, open-label trial was conducted at The University of Texas MD Anderson Cancer Center in Houston and enrolled a total of 35 patients from October 31, 2019, to March 25, 2021. Most patients (77%) had colorectal adenocarcinomas, which included colon adenocarcinoma (54%), rectal adenocarcinoma (23%), pancreatic adenocarcinoma (6%), duodenal adenocarcinoma (6%), and other (11%).

Patients had unresectable cancer at a rate of 26%, with 74% of patients presenting with clinical stage 3 disease and 23% with stage 2 disease. Additionally, 74% of patients were not previously treated and 11% of patients had prior radiation, 9% surgery, and 6% chemotherapy.

The coprimary end points were safety and pCR. Key secondary end points included ORR and organ-sparing at 1 year for patients who declined surgery.

Pembrolizumab 200 mg was administered intravenously once every 3 weeks for 8 treatments followed by surgical resection. A nonsurgical management option included was for patients to receive pembrolizumab for 16 treatments followed by observation.

Eligible patients were at least 18 years of age with measurable disease by RECIST 1.1 with locally advanced, defined as a 20% chance or greater of recurrence with solely surgical resection, dMMR/MSI-H solid cancers. The median age was 62 years (range, 25-90) and more than half of patients were women (57%). Limitations of the study design included the small patient population, enrollment at only 1 institution, and the choice given to the patient and/or treating physician to decide whether to proceed with surgical resection.

Thirty patients (86%) in the trial had luminal gastrointestinal cancers. Additional findings from the study showed that among the 19 who were evaluable for endoscopic response, 63% experienced a CR and 37% had incomplete responses with a median time to response of 17 weeks (range, 6-31). Five patients who had a CR underwent surgical resection, all of whom achieved a pCR. Additionally, 3 of the patients who had incomplete responses underwent surgical resections with 2 experiencing a pCR and 1 residual disease.

Moreover, 19 patients had serial sample and detectable circulating tumor DNA (ctDNA) at baseline and 13 of 15 patients with ctDNA decrease had no progression. The study authors noted that an early decrease in ctDNA was predictive of no future progression events (

No new safety signals were reported for pembrolizumab. Grade 1 or 2 adverse events (AEs) occurred in 37% of patients in the safety population (n = 35) and 6% experienced grade 3 AEs. No grade 4 AEs were reported. Out of the 17 patients who underwent surgery, 3 postoperative complications were experienced consisting of grade 3b surgical site abscess, grade 1 abdominal wall hematoma, and grade 2 diarrhea occurring.

Pembrolizumab was previously granted accelerated approval by the FDA on May 23, 2017, for the treatment of adult and pediatric patients with unresectable or metastatic, MSI-H/dMMR solid tumors whose disease had progressed after prior treatment.2 Additionally, the PD-1–targeted antibody gained a standard approval from the agency for the first-line treatment of patients with unresectable or metastatic MSI-H/dMMR colorectal cancer on June 29, 2020.

MSI-H and dMMR tumors are most commonly found in colorectal, endometrial, and gastric cancers and are typically seen in the early-stage of disease. Although therapy for localized dMMR cancer is based on treatments for proficient MMR/microsatellite stable tumors which includes surgery, chemotherapy, and/or radiation, data have indicated that chemotherapy may not provide the same level of benefit for dMMR disease.

MSI-H tumors, regardless of PD-L1immunohistochemistry expression levels, have had greater responses to checkpoint blockades with PD-1 or PD-L1 inhibitors than microsatellite stable tumors.

 Additionally, dMMR tumors have a high prevalence in colorectal adenocarcinomas; an analysis of 16,065 evaluable biopsy specimens demonstrated an overall dMMR prevalence of 13.4% compared with only 2.7% within the rectal cancer subset.

“When the immune profiles between progressors and nonprogressors were compared, progressors demonstrated a trend toward higher presence of granulocytic cell cluster and exhausted T cells…the presence of CD151 granulocytic cell types and their close proximity to CD81 T cells associate with progression in dMMR cancers,” study authors noted. 

Future directions for this research include further investigating checkpoint inhibitors, which have established efficacy in this patient population, in the neoadjuvant space as well as enrolling larger studies on dMMR solid tumors to define duration of therapy. The best assessment to evaluate luminal tumors also requires more investigation according to the study authors.

Ludford K, Ho WJ, Thomas JV, et al. Neoadjuvant pembrolizumab in localized microsatellite instability high/deficient mismatch repair solid tumors. 

. Published online January 9, 2023. doi:10.1200/JCO.22.01351

Ciombor KK, Eng C. Immunotherapy in localized microsatellite instability-high/mismatch repair deficient solid tumors: are we ready for a new standard of care? 

. Published online January 9, 2023. doi:10.1200/JCO.22.02564

FDA approves pembrolizumab for first-line treatment of MSI-H/dMMR colorectal cancer. FDA. Updated June 30, 2020. Accessed January 25, 2023. bit.ly/3XXORkO

Marginean EC, Melosky B. Is there a role for programmed death ligand-1 testing and immunotherapy in colorectal cancer with microsatellite instability? Part II-the challenge of programmed death ligand-1 testing and its role in microsatellite instability-high colorectal cancer. 

. 2018;142(1):26-34. doi:10.5858/arpa.2017-0041-RA

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