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Report from the 2024 American Society of Hematology Annual Meeting — Malignant Hematology
NEJM Group was on hand to cover the 2024 American Society of Hematology (ASH) annual meeting, held December 7 to 10 in San Diego. Here, NEJM Journal Watch Oncology and Hematology reports some of the key findings in hematologic malignancies, and Associate Editor Dr. Michael E. Williams provides clinical perspective.
In patients with relapsed or refractory follicular lymphoma, the addition of tafasitamab to lenalidomide plus rituximab improves progression-free survival (PFS), according to the industry-funded, phase 3 inMIND trial. Tafasitamab, a humanized CD19-targeting monoclonal antibody, is currently approved in combination with lenalidomide for the treatment of relapsed or refractory diffuse large B-cell lymphoma.
Roughly 550 adult patients with relapsed or refractory follicular lymphoma after at least one prior line of systemic therapy that included an anti-CD20 monoclonal antibody were randomized to receive either intravenous tafasitamab (12 mg/kg) or placebo plus lenalidomide and rituximab for up to 12 cycles. During a median follow-up of 14 months, the risk of progression, relapse, or death was significantly lower with tafasitamab than with placebo (hazard ratio, 0.43), with a median PFS of 22 versus 14 months. There was also a trend toward an overall survival benefit with tafasitamab, but the data were immature.
Rates of treatment-emergent adverse events, grade 3 or 4 adverse events, and serious adverse events were similar in the two groups.
The researchers note that the regimen “can be administered in community as well as academic settings and represents a potential new standard of care option” for patients with relapsed or refractory follicular lymphoma.
Summary by Amy Herman, Staff Editor
COMMENT — Dr. Michael Williams
This practice-changing study establishes a significant PFS benefit for dual monoclonal antibodies targeting CD19 and CD20 plus the immunomodulatory agent lenalidomide. Notably, toxicities did not differ with the addition of tafasitamab, and only 7%–11% of patients discontinued treatment in either arm due to adverse events.
The addition of the monoclonal antibody blinatumomab to standard chemotherapy is associated with prolonged disease-free survival in pediatric patients with standard-risk B-cell acute lymphoblastic leukemia (ALL), according to a phase 3 trial presented at the meeting and published in the New England Journal of Medicine.
Patients aged 1 to 9 years with newly diagnosed standard-risk B-cell ALL received a three-drug induction. Over 1400 patients who were subsequently stratified as having an average or high relapse risk were randomized to receive either chemotherapy alone or chemotherapy plus two nonsequential cycles of intravenous blinatumomab for 28 days.
The primary endpoint of disease-free survival was significantly higher in those who received blinatumomab (3-year post-randomization: 96% for blinatumomab vs. 88% for chemotherapy alone). The positive effect was observed in both average- and high-risk patients. After seeing these interim efficacy results, the data safety and monitoring committee recommended that randomization be stopped early.
Among average-risk patients, grade 3 or higher sepsis and catheter-related infections were more common in the blinatumomab group than in the chemotherapy group (15% vs. 5%).
Summary by Kelly Young, Staff Editor
COMMENT — Dr. Michael Williams
This practice-changing study shows further improvement in outcomes for childhood B-cell ALL, with nearly 100% of those at average relapse risk and over 90% of those considered at high risk of relapse remaining disease-free at 3 years after randomization. Acute bispecific toxicities were manageable, but attention to ongoing infection risk is warranted.
In patients with high-risk smoldering (asymptomatic) multiple myeloma, the monoclonal antibody daratumumab significantly delays progression to active myeloma, according to findings from the phase 3, manufacturer-sponsored AQUILA trial, presented at the conference and published in the New England Journal of Medicine. Daratumumab is approved to treat active multiple myeloma.
Nearly 400 patients were randomized to receive daratumumab or active monitoring alone. The daratumumab group received 1800 mg subcutaneously for 39 cycles, 36 months, or until progression occurred.
During a median 65-month follow-up, the daratumumab group had about half the risk of progression or death relative to the monitoring group, a significant difference (hazard ratio, 0.49). At 5 years, progression-free survival rates were 63% and 41%, respectively. Five-year overall survival, a secondary outcome, also was better with daratumumab (93% vs. 87%), although follow-up is ongoing.
No new safety issues arose. Serious adverse events occurred in 29% with daratumumab and 19% with monitoring, and grade 3 or 4 adverse events in 40% and 30%, respectively.
Summary by Christine Sadlowski, Staff Editor
COMMENT — Dr. Michael Williams
Smoldering myeloma, defined according to International Myeloma Working Group criteria, has a relatively short time to overt myeloma and related complications when higher-risk features are present. The long duration of follow-up in this study confirms a significant progression-free survival benefit with single-agent daratumumab immunotherapy, as well as a trend toward improved overall survival, with no unexpected toxicities.
For younger patients with mantle-cell lymphoma (MCL), ibrutinib-containing regimens — with or without autologous stem-cell transplantation (ASCT) — result in better survival outcomes than chemoimmunotherapy plus ASCT, according to longer-term follow-up from the industry-funded, international TRIANGLE trial.
Nearly 900 patients age 65 years and younger with previously untreated, stage II to IV MCL who were candidates for high-dose cytarabine and ASCT were randomized to one of three regimens: six alternating cycles of R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) and R-DHAP (rituximab, dexamethasone, cytarabine, and cisplatin) followed by ASCT (arm A); the same regimen with ibrutinib added during R-CHOP and for 2 years of maintenance therapy after ASCT (arm A+I); or ibrutinib added during R-CHOP and as maintenance therapy but without ASCT (arm I).
Among the findings, after a median follow-up of roughly 4.5 years:
Failure-free survival: Three-year failure-free survival was 75% in arm A, 86% in arm A+I, and 85% in arm I. Failure-free survival was superior with the two ibrutinib-containing regimens than with chemoimmunotherapy plus ASCT, and the two ibrutinib-containing regimens were similarly effective regardless of ASCT use.
Overall survival: Three-year overall survival was 85% in arm A, 90% in arm A+I, and 91% in arm I. Again, findings favored the two ibrutinib-containing regimens, with no significant difference between the two.
The authors conclude, “Ibrutinib+R-CHOP/R-DHAP induction followed by 2 years of ibrutinib maintenance should be the new standard of care in younger MCL patients, thus ending the era of ASCT for MCL patients.”
Summary by Amy Herman, Staff Editor
COMMENT — Dr. Michael Williams
With longer follow-up since the initial TRIANGLE presentation in the ASH 2022 Plenary Session, and with the study's original publication in The Lancet, a significant survival advantage has emerged for the ibrutinib-containing arms versus standard induction and ASCT. As such, the routine use of ASCT consolidation is no longer the standard of care. It remains to be seen if ibrutinib's MCL indication will be restored in the U.S. as a result of this report, or if alternative Bruton's tyrosine kinase (BTK) inhibitor agents will be utilized. (Also recommended for your review are the results of ibrutinib with or without rituximab as maintenance therapy in TRIANGLE, reported in the same ASH 2024 session.)
Read more about the latest TRIANGLE findings.
For patients with mantle-cell lymphoma (MCL) who are in first complete remission with undetectable minimal residual disease (MRD), autologous stem-cell transplantation (ASCT) does not appear to improve survival, according to a planned interim analysis from the phase 3 ECOG-ACRIN EA4151 trial.
More than 500 adults who achieved first remission and had undetectable peripheral blood MRD by molecular testing (at 1 cell in 10-6 sensitivity) after induction were randomized to receive either ASCT plus 3 years of maintenance rituximab or maintenance rituximab alone.
Overall survival, the primary endpoint, did not differ significantly between the two groups at 3 years (82% with ASCT and 83% with rituximab alone). Results were similar for progression-free survival at 3 years (77% of each group).
The study also assessed roughly 50 patients who were MRD-positive following induction and received ASCT plus 3 years of maintenance rituximab. At 3 years, overall survival was 82% in all patients and 100% among the 17 patients who converted to undetectable MRD after ASCT. The researchers note that this group might benefit from consolidative transplantation.
Summary by Kelly Young, Staff Editor
COMMENT — Dr. Michael Williams
ASCT consolidation and maintenance rituximab has been a standard of care for younger patients with MCL, with the aim of prolonging remission. This important U.S. Cooperative Group trial is the first MRD-driven MCL trial, testing whether high-dose therapy and ASCT are needed if patients have achieved PET-negative and MRD-undetectable remission following induction therapy. Taken together with the TRIANGLE data presented at ASH, ASCT consolidation and associated risks can be avoided with the use of a Bruton's tyrosine kinase (BTK) inhibitor in frontline therapy, and in those achieving deep response to induction therapy.
Among patients with acute myeloid leukemia (AML), certain markers of socioeconomic status — in particular, lower education level and receipt of nutrition assistance — are associated with a lower likelihood of receiving allogeneic hematopoietic cell transplantation (HCT), according to findings from a prospective, multicenter, observational study.
Using information on the ZIP codes in which some 700 patients with AML lived, researchers examined potential associations between numerous socioeconomic factors and receipt of HCT. Among the findings, after multivariable adjustment:
High school education: The likelihood of receiving HCT decreased by 32% for every 10% increase in the percentage of neighborhood residents aged 25 or older with less than a high school education.
Food stamps: The likelihood of HCT decreased by 14% for every 10% increase in the percentage of households receiving Supplemental Nutrition Assistance Program (SNAP).
Income: Median income was not significantly associated with HCT receipt or post-HCT mortality.
Given the association between education level and HCT receipt, the researchers conclude that the main issue may be access to HCT.
Summary by Amy Herman, Staff Editor
COMMENT — Dr. Michael Williams
Disparities in access to specialized cancer care have been increasingly recognized, challenging our profession and institutions to address unmet needs. Assuring that state-of-the-art care and advanced therapeutics, including clinical trial access, is made available to both rural areas and underserved urban sites, as well as to those with socioeconomic, ethnic, and racial barriers, must be prioritized.
Empfohlen von
Michael E. Williams, MD, ScM