Late-Breaking Abstracts at EHA2022 Describe Therapy Comparisons, Investigational Treatments in Hematology

The late-breaking oral session at the 2022 European Hematology Association (EHA) Congress allowed investigators to present recently emerging data from abstracts submitted after the deadline. The presentations included outcomes from the phase 3 GAIA trial in chronic lymphocytic leukemia (CLL), the phase 3 DETERMINATION trial in multiple myeloma, and a study of a single-dose treatment for transfusion-dependent beta-thalassemia and severe sickle cell disease (SCD).

Phase 3 DETERMINATION Trial in Newly Diagnosed Multiple Myeloma

This presentation by Paul Richardson, MD, of Dana-Farber Cancer Institute, focused on results of the 56-site trial on the impact of allogeneic stem cell transplant (ASCT) in conjunction with lenalidomide (Revlimid), bortezomib (Velcade), and dexamethasone (RVd) triple therapy in multiple myeloma. Among 357 patients who received RVd alone and 365 who received RVd and ASCT, the investigators observed a significant advantage in progression-free survival (PFS) among those with both RVd and ASCT, at 67.5 months vs 46.2 in those receiving just RVd (HR of PFS with ASCT, 1.53). However, there was no overall survival (OS) benefit with ASCT, and the rate of hematologic secondary second primary malignancies was higher in the ASCT group.

Richardson noted some trends that are not definitive due to small sample sizes but nonetheless intriguing, namely that subgroups of African American participants and those with a high body mass index had narrower HRs of the PFS end point. He called for further research on these hypothesis-generating patterns, as well as studies of ASCT and RVd with longer follow-up.

PFS in Phase 3 GAIA/CLL13 Trial

Barbara Eichhorst, MD, of the University Hospital Cologne, presented data on the end point of PFS in this 4-arm study of fit patients with CLL that compared obinutuzumab and venetoclax (Gazyva and Venclexta; GV) with or without ibrutinib (GV + ibrutinib, GIV) vs chemoimmunotherapy (CIT) in the first line of treatment. Findings revealed last year showed the superiority of GV and GIV vs CIT in terms of the undetectable minimal residual disease end point, and Eichhorst presented new data confirming that the end point of PFS was also met, with HRs of progression of 0.32 for GIV and 0.42 for GV vs CIT over a median follow-up of 38.8 months.

In response to an audience question about whether ibrutinib adds enough efficacy to warrant its inclusion the regimen given its tendency to increase the risk of infection, Eichhorst explained that a head-to-head comparison of GV vs GIV is forthcoming and data may be presented at next year’s congress.

Single-Dose CTX001 for Transfusion-Dependent Βeta-Thalassemia and Severe SCD

Next, Franco Locatelli, MD, PhD, of the University of Rome, presented findings on the safety and efficacy of CTX001 (exa-cel), a cell therapy that uses CRISPR/Cas-9–mediated editing of BCL11A to increase hemoglobin levels in erythroid cells. Among 44 patients with transfusion-dependent beta-thalassemia (TDT) and 31 patients with severe SCD, CTX001 appeared to be effective and well tolerated, meeting its primary end points in both study groups. After a median follow-up of 11.9 months, 42 of the 44 patients with TDT were transfusion free, and the remaining 2 experienced reductions of 75% and 89% in transfusion volume, respectively. All patients with SCD were free of vaso-occlusive crises after a median follow-up of 10.2 months.

Locatelli noted that these findings demonstrate “successful and durable” editing of long-term hematopoietic stem cells, indicating CTX011’s potential to offer a functional cure to patients with these hematological conditions.

Evolutionary Landscape of Clonal Hematopoiesis in Older Individuals

Isabelle van Zeventer, PhD candidate at University Medical Center Groningen, presented findings on a cohort of 3359 community-based older participants to examine the age-related emergence of clonal hematopoiesis (CH), which occurs when peripheral blood cells undergo genetic changes that may increase the risk of hematologic malignancy. She explained that individuals with existing CH at baseline had a higher risk of acquiring new mutations, and by linking the cohort’s data to the national cancer registry of the Netherlands, the investigators identified 74 new malignancies (35 myeloid, 39 lymphoid) over a median of 7.7 years of follow-up.

Different mutational features of CH are associated with different levels of risk, so clinicians may want to consider monitoring or intervention for those with a high-risk mutational pattern, van Zeventer said. Interestingly, traditional cancer risk factors such as smoking and overweight had no effect on clonal growth and mutation.

Phase 3 Findings of Leniolisib in Patients With Activated PI3K Delta Syndrome

V. Koneti Rao, MD, of the National Institutes of Health, delivered his presentation virtually from Bethesda, Maryland, in which he detailed findings of the investigational drug leniolisib in patients with the rare activated PI3K delta syndrome, which can result in lymphoproliferation, infections, and gastrointestinal, lung, and liver disease. In the trial of 31 patients randomized to receive leniolisib or placebo for 12 weeks, the investigational drug increased the proportion of naïve B cells and reduced lymphadenopathy (ie, size of index lymph nodes), whereas lymph node size tended to increase in the placebo group.

Leniolisib was associated with transient neutropenia that then resolved, and was otherwise well tolerated, with a serious adverse event rate lower than that of the placebo arm. Rao noted that the research group is now offering enrollment in an open-label extension trial given these encouraging findings.

Comparing Regimens in High-risk Burkitt Lymphoma

Finally, Martine Chamuleau, MD, PhD, of Amsterdam University Medical Center, presented results from the first randomized prospective trial comparing 2 chemotherapy regimens in high-risk Burkitt lymphoma. In arm A, patients received either cyclophosphamide, doxorubicin, vincristine, rituximab, and methotrexate (R-CODOX-M) or etoposide, ifosfamide, cytarabine, and rituximab (R-IVAC); in arm 2, they received rituximab, etoposide, doxorubicin, vincristine, prednisolone, and cyclophosphamide (DA-EPOCH-R). The PFS and OS outcomes were similar in both arms, with slight but nonsignificant advantages in favor of R-CODOX-M and R-IVAC (PFS: P = .38; OS: P = .85). However, patients receiving R-CODOX-M or R-IVAC experienced greater toxicity and more infectious serious adverse events and more often required transfusions or hospitalization compared with patients receiving DA-EPOCH-R.

Thus, Chamuleau concluded that given the comparable survival outcomes, the DA-EPOCH-R regimen appears to be preferable given its lower risk of toxicity.

As the session drew to a close, chair Kirsten Grønbæk, MD, University of Copenhagen, announced the winner of the EHA bowling competition (Frank Leebeek, MD, PhD, of Erasmus University in Rotterdam) and thanked the attendees for “coming to Vienna and making this such a wonderful conference.”