Advances in the treatment of hematologic malignancies and some of their associated symptoms were presented during EHA25 Virtual, an ongoing online conference from the European Hematology Association (EHA).
Advances in the Treatment of High-Risk CLL: CLL2-GIVe Results
In the CLL2-GIVe trial, the German CLL study group evaluated a new first-line therapy regimen for patients with high-risk chronic lymphocytic leukemia (CLL) and a 17p deletion and/or TP53 mutation (Abstract S157).
Patients enrolled in the study received the triplet combination of obinutuzumab, venetoclax and ibrutinib for 6 months, followed by the combination of venetoclax and ibrutinib for another 6 months. Subsequently, ibrutinib maintenance therapy was given if undetectable minimal residual disease (MRD) and complete remission according to International Workshop on Chronic Lymphocytic Leukemia criteria had not been achieved by then.
The rate of complete remissions reported was 58.5%. In 80.5% of patients, MRD was undetectable in peripheral blood at cycle 15. The safety profile was acceptable.
The study authors concluded, “The GIVe triple combination regimen is a promising first-line treatment option for pts with high-risk CLL yielding encouraging response rates and 80.5% undetectable MRD.”
PET-Guided Therapy in Early-Stage Unfavorable Hodgkin Lymphoma
For decades, combined modality treatment comprising four cycles of chemotherapy and radiotherapy has been the standard of care for patients with early-stage Hodgkin lymphoma with risk factors indicating an unfavorable prognosis. Combined modality treatment produces good responses in this population; however, the use of radiotherapy in this young patient group (median age = 30 years at disease onset) raises concerns regarding adverse events in the long term, such as cardiovascular disease and secondary malignancies.
The HD17 study (Abstract S101) investigated if radiotherapy can be omitted from combined modality treatment for patients that respond well to chemotherapy, as determined by fluorodeoxyglucose F-18 (FDG)–positron-emission tomography (PET); 1,100 patients were enrolled into this European, prospective, randomized trial.
The HD17 trial has proven that omission of radiotherapy does not result in a loss of tumor control in patients responding well to a standard chemotherapy regimen. At 5 years follow-up, 2 of 1,100 patients died from Hodgkin lymphoma and only 1 died from treatment-emergent adverse events.
The mortality of patients with early-stage unfavorable Hodgkin lymphoma in the HD17 study did not differ from the normal German population. The study authors concluded that combined modality treatment can and should be replaced by a PET-guided omission of radiotherapy for patients with newly diagnosed early-stage unfavorable Hodgkin lymphoma.
Combined Irradiation and Chemotherapy vs Chemotherapy Alone Before Pediatric Stem Cell Transplant
More than 90% of patients with acute lymphoblastic leukemia (ALL) younger than 18 are treated successfully with contemporary chemotherapy. However, the remaining 10% have resistant or recurrent leukemia and require alternative treatment regimens. One of the most effective therapies for leukemia therapies is allogeneic hematopoietic stem cell transplantation (HSCT). Approximately 50% to 80% of pediatric patients with ALL patients that receive allogeneic HSCT are cured; 20% experience relapsed disease, and 10% die from complications.
Allogeneic HSCT requires multiple steps:
- Identify a suitable donor.
- Reduce the patient's leukemia to an undetectable level with chemotherapy, antibodies, or chimeric antigen receptor T cells.
- Collect a donor graft by harvesting bone marrow, peripheral blood stem cells, or umbilical cord blood.
- Prepare the patient for transplant (“conditioning”).
- Perform the transplant.
For high-risk leukemia, the gold standard conditioning procedure is a combination of total-body irradiation and high-dose chemotherapy. This approach is effective in controlling leukemia in the conditioning step, but patients may experience negative consequences of this procedure later in life, such as issues with fertility and growth, pulmonary problems, and secondary malignancies.
Therefore, a large consortium of pediatric transplant experts initiated a global study to investigate whether chemotherapy-based conditioning could substitute total-body irradiation (Abstract S102). The study is called FORUM (For Omitting Radiation Under Majority Age) and had to be stopped because chemotherapy-based conditioning had significantly poorer outcomes (ie, lower overall survival rates) than the combination of total-body irradiation and chemotherapy. The researchers will now perform prospective monitoring to better define the advantages and limitations of various conditioning approaches.
Imetelstat, a Novel Telomerase Inhibitor, in Patients With Lower-Risk Myelodysplastic Syndromes
IMerge is a phase II/III clinical trial evaluating imetelstat as a treatment for patients with lower-risk myelodysplastic syndromes (MDS) that are non-del(5q), dependent on red blood cell transfusion, and are relapsed after or refractory to treatment with erythropoiesis-stimulating agents (Abstract S183).
The primary efficacy endpoint of IMerge is 8-week red blood cell transfusion independence rate, defined as the proportion of patients not receiving any red blood cell transfusion during any consecutive 8 weeks since entry into the trial. The presentation at EHA25 Virtual reported long-term efficacy and safety data from 38 patients in phase II of IMerge, based on a February 4, 2020, cutoff date and a median follow-up of 24 months.
- Sixteen patients (42%) achieved 8-week red blood cell transfusion independence rate, and 12 of these responders (75%) showed a hemoglobin rise > 3 g/dL compared to pretreatment during the transfusion-free interval.
- Twelve patients (32%) achieved a 24-week red blood cell transfusion independence rate.
- Eleven patients (29%) were transfusion-free for more than 1 year; the longest transfusion-free interval was 2.7 years.
- Median red blood cell transfusion independence rate duration was 88 weeks, the longest reported to date in non-del(5q) lower-risk MDS.
- Hematologic improvement–erythroid was achieved by 26 patients (68%) with a median duration of 93 weeks.
- Durability of transfusion independence as well as cytogenetic and mutational malignant clone reduction in some patients indicates potential disease-modifying activity of imetelstat.
- The most frequently reported adverse events were manageable and reversible grade > 3 cytopenias.
The phase III double-blind, placebo-controlled stage of IMerge is ongoing and currently recruiting patients.
Ruxolitinib for Steroid-Refractory Acute GVHD: Follow-up of the REACH2 Trial
Acute graft-vs-host disease (GVHD) remains a major limitation of allogeneic stem cell transplantation; not all patients respond to standard treatment with steroids. In the recent phase III REACH2 trial, ruxolitinib improved outcomes in patients with steroid-refractory acute GVHD. The study, which included 309 patients, showed that a higher percentage of patients responded to ruxolitinib than standard therapy after 28 days of treatment (62.3% vs 39.4%; P < .001). Detailed results were published in The New England Journal of Medicine in May 2020.
In this follow-up analysis (Abstract S255), researchers explored responses in different subgroups of patients of the REACH2 trial. Patient subgroups were formed based on various patient characteristics recorded at the start of the study.
Several subgroups of patients responded better to ruxolitinib than to standard therapy, including:
- Patients aged 18 to 65 years
- Patients who did not respond to or had disease progression on high doses of steroids
- Patients with varying degrees of disease severity, organ involvement, related or unrelated donor, and prior GVHD therapy.
Additionally, when compared with standard therapy, a higher percentage of patients treated with ruxolitinib had a response at day 28 and maintained response at day 56 (39.6% vs 21.9%; P < .001). No new or unexpected safety concerns were observed.
The study authors concluded, “Ruxolitinib showed a consistent clinically meaningful treatment benefit for patients with steroid-refractory acute GVHD across different subgroups of baseline characteristics.”
Disclosures: For full disclosures of the study authors, visit library.ehaweb.org.
