64th ASH Annual Meeting and Exposition: Broad Coverage of Clinical, Social, and Nutritional Issues

At the 64th American Society of Hematology (ASH) Annual Meeting and Exposition held in New Orleans, Louisiana, ASH Secretary Cynthia E. Dunbar, MD, explained that the focus of this meeting was more on the long-term impact of both novel targeted therapies and cell and gene therapy on patients, including financial toxicity, patient-reported outcomes and quality of life. “As we come up with better and better scientifically supported and active treatments, [we have] to figure out which ones are really worth it, and which ones are the best, long term,” said Dunbar. 

Beginning with Health Equity

The annual meeting kicked off with a variety of health equity issues, including racial disparities in the treatment of pulmonary embolism with various advanced therapies, an examination of how lab-based inclusion criteria in clinical trials for diffuse large B-cell lymphoma affect the participation of non-White patients, and an analysis of how the relationship between non-European ancestry and low socioeconomic status plays a role in matching allograft recipients for bone marrow transplantation. Research findings were also presented on the global increase in the use of hematopoietic stem cell transplants for acute myeloid leukemia that is not being felt evenly across patient populations.

Advancements in Trials Targeting Multiple Myeloma and B-cell Lymphoma

The first day of the meeting also featured recent research findings in the treatment of refractory diseases, including ADVANCE IV, a Phase 3 randomized, double-blind and placebo-controlled trial of intravenous efgartigimod, a novel treatment for refractory primary immune thrombocytopenia.

Talquetamab is an investigational bispecific antibody targeting both CD3 receptors on T cells and G protein-coupled receptor family C, group 5, member D (GPRC5D) on tumor cells of multiple myeloma (MM). Results from the MonumenTAL-1 a Phase 1/2 dose escalation study of talquetamab in participants with relapsed/refractory MM, demonstrated that this bispecific antibody can bind to both tumor cells and T cells to facilitate MM tumor cell killing by T cells.

The ongoing BGB-3111-215 Phase 2 trial (NCT04116437) is evaluating the safety of zanubrutinib in previously treated patients with B-cell lymphoma who are intolerant to prior therapy with Bruton’s tyrosine kinase (BTK) inhibitors such as ibrutinib or acalabrutinib. Recent findings from this study, presented at the 2022 ASH Annual Meeting, showed that the median duration of zanubrutinib treatment was 7.6 months compared with 4.6 months for patients receiving acalabrutinib. Even though patients were treated with zanubrutinib for a longer period of time, 67% of them did not experience a recurrence of adverse reactions that caused intolerance to acalabrutinib. Moreover, no higher-level adverse reactions were observed with zanubrutinib treatment compared to acalabrutinib. It is also noteworthy that the disease control rate (DCR) and the overall response rate (ORR) of zanubrutinib treatment were found to be 94% and 61% respectively, meaning that patients would be able to continue to experience the benefits of zanubrutinib.

In a separate Phase 2 study of zanubrutinib, the MAGNOLIA trial in patients with relapsed/refractory (R/R) marginal zone lymphoma also showed consistently high response rates (an ORR of 68.2%) and durable disease control with a favorable safety profile characterized by lower rates of hypertension and atrial fibrillation.

Other Compelling Findings for Hematological Malignancies

Researchers from The University of Texas MD Anderson Cancer Center presented findings from a Phase 2 trial on a combination of ponatinib and blinatumomab for newly diagnosed patients with Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL). According to Nicholas J. Short, MD, one of the lead investigators of this study, the combination was shown to achieve high response rates and reduce the need for allogeneic hematopoietic stem cell transplantation (HSCT) at first remission in patients with recently diagnosed Ph+ acute ALL. 

In another Phase 3 study called ALPINE comparing zanubrutinib with ibrutinib as treatment for relapsed/refractory chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL), zanubrutinib demonstrated higher overall response rate and better progression-free survival in participants with R/R CLL or SLL. Besides, zanubrutinib had a favorable safety profile when compared with ibrutinib, with a lower rate of treatment discontinuation and fewer adverse cardiac events. While Dunbar commented that ibrutinib was a “revolutionary drug” for the treatment of CLL, it is not effective for all patients, and it also has some significant side effects, particularly to the heart. 

Data Presentation in Less-studied but Important Areas

Issues related to women and children or nutritional supplementation have been less studied in the clinical arena, but there were several reports presented at this ASH meeting that could deserve attention. One example was the Phase 3 ALIFE2 study, which examined the use of low-molecular-weight heparin versus standard pregnancy care for women with recurrent miscarriage and inherited thrombophilia. The trial results presented focused on the 5% of women with recurrent pregnancy loss that have specific situations known to cause increased risk of venous thrombosis, regardless of whether they were pregnant or not. Disappointingly, results showed that low-molecular-weight heparin was not found to improve miscarriage rates. In spite of such a setback, Dunbar believed that this study provided definitive results for the screening and treatment of women in this situation.

Another example was a study that made use of long-term data from St. Jude Children’s Hospital to evaluate how treatment for pediatric Hodgkin lymphoma (HL) could affect patients’ neurocognitive function over their lifetime. The study focused on the epigenetic age acceleration (EAA) in pediatric HL survivors (higher EAA suggested older biological age relative to chronological age), which could serve as an important biomarker that might predict the risk of early onset dementia in these survivors.

Concerning nutritional issues, an Italian study examined the effectiveness of a neutropenic diet for patients undergoing stem cell transplantations such as HSCT, a kind of protective diet traditionally used to reduce the risk of foodborne infections during the first weeks or months after transplantation. Interestingly, according to the results presented in the ASH annual meeting, there was no significant difference in terms of cumulative rates of infections when comparing patients with neutropenic diets following HSCT to those having non-restrictive diets. These findings demonstrated that the use of neutropenic diets might impose an unnecessary burden on patients’ quality of life without reducing infection incidence, suggesting that it would be acceptable for patients to enjoy the foods they prefer. 

Author

Richard Chau

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