Below are summaries of recently published analyses of studies led by the ECOG-ACRIN Cancer Research Group. Click on the shortened citation to access the publication.

Leukemia – Relapsed B-cell or T-cell acute lymphoblastic leukemia (ALL) remains a therapeutic challenge, especially in older or unfit patients who may not be eligible for cellular therapies. The Phase 1b/2 clinical trial EA9152 is investigating venetoclax, a BCL-2 inhibitor, in combination with vincristine sulfate in this patient population. Venetoclax is FDA-approved for various hematologic malignancies but remains experimental for ALL. Phase 2 of EA9152 is currently active after the first part of the trial found the combination to have an acceptable safety profile. A phase 1 trial of venetoclax in combination with liposomal vincristine in patients with relapsed or refractory B-cell or T-cell acute lymphoblastic leukemia: Results from the ECOG-ACRIN EA9152 protocol. Palmisiano ND. Eur J Haematol. August 2024

Leukemia – The US Food & Drug Administration approves using ibrutinib and rituximab (IR) in combination for the frontline treatment of patients aged 70 and younger with chronic lymphocytic leukemia (CLL). This approval is based on the practice-changing randomized phase 3 trial E1912, which eliminated the need for chemotherapy in these patients (Shanafelt TD. N Engl J Med. 2019). Since then, frontline treatment for these patients has continued to evolve. Here, Dr. Shanafelt and colleagues report the latest long-term data from E1912: Tolerability and long-term disease control by IGHV mutation status among CLL patients on the ibrutinib arm of E1912. Shanafelt TD. Blood Advances. August 2024

Leukemia – B-cell acute lymphoblastic leukemia occurs across all age groups, with a strikingly higher cure rate in children compared with adults. In this analysis, ECOG-ACRIN researchers studying the disease in adults collaborated with pediatric researchers to systematically characterize the associations between drug response and ALL genomics in children, adolescents and young adults, and elderly adults. Impact of Age on Pharmacogenomics and Treatment Outcomes of B-cell Acute Lymphoblastic Leukemia. Yoshimura S. J Clin Oncol. August 2024 (subscription required)

Lymphoma – "More is not always better," says Carlo Visco (University of Verona) in an editorial that accompanies the final results of trial E1411, Randomized study of induction with bendamustine-rituximab ± bortezomib and maintenance with rituximab ± lenalidomide for MCL. While initial therapy for mantle cell lymphoma (MCL) is not standardized, bendamustine-rituximab (BR) is commonly used in older patients. Rituximab (R) maintenance following induction is often utilized. E1411 was a randomized phase 2 trial in patients aged 60 and above with previously untreated MCL. It found that adding bortezomib to BR induction did not prolong PFS, and LR maintenance was not associated with longer PFS. The > 5-year median PFS outcomes in this prospective trial indicate the efficacy of BR followed by rituximab maintenance as a highly effective initial therapy for older MCL patients. Further, this regimen can be considered the preferable comparator for developing new treatments for these patients. Smith MR. Blood. September 2024 (subscription required)

Prostate Cancer – Androgen deprivation therapy (ADT) with docetaxel (D) and/or antiandrogen receptor therapies (ARTs) are the standard treatments for patients with metastatic hormone-sensitive prostate cancer (mHSPC). The tumor suppressor genes RB1, PTEN, and TP53 are known to be associated with aggressive disease and treatment resistance in patients with castration-resistant prostate cancer. Here, researchers conducted a retrospective biomarker analysis of these mutations using data from the CHAARTED (E3805) trial in patients with mHSPC. Development and Independent Validation of a Prognostic Gene Expression Signature Based on RB1, PTEN, and TP53 in Metastatic Hormone-sensitive Prostate Cancer Patients. Jimenez N. Eur Urol Oncol. August 2024