Get up-to-date on the most recent data presented on CLL and CML treatment from the 2017 American Society of Clinical Oncology (ASCO) annual meeting.
Bosutinib Is More Effective Than Imatinib in Newly Diagnosed CML
Results from the randomized open-label phase III BFORE trial (Abstract 7002) involving 536 patients with treatment-naïve chronic phase chronic myeloid leukemia (CP CML), showed that the dual Src/Abl tyrosine kinase inhibitor (TKI) bosutinib 400 mg daily significantly improved major molecular response (MMR) rates at 12 months compared with imatinib 400 mg daily (47.2% vs 36.9% respectively; P = .02) Of note, the MMR rate at 12 months was higher with bosutinib in all Sokal risk groups (high: 34% vs 17%; intermediate: 45% vs 39%; low: 58% vs 46%). In addition, 75% of patients on bosutinib compared to 57% on imatinib achieved early molecular responses (BCR-ABL1 transcript levels were ≤10% at 3 months). Bosutinib also improved rates of complete cytogenetic response (CCyR) at 12 months (77.2% vs 66.4%; P<.01) and yielded deeper responses at 12 months (MR4.5: 8.1% vs 3.3%). The event-free survival and overall survival are not yet mature, but there was numerically fewer events with bosutinib. Bosutinib was associated with increased rates of diarrhea and transaminase elevation compared with imatinib, while imatinib was associated with a higher rate of musculoskeletal events and periorbital edema. Presenter Jorge Cortes, MD (MD Anderson Cancer Center, Houston, Texas, United States), highlighted that lower dose of bosutinib (400 mg) is associated with better tolerability and improved outcomes, and he concluded that based on these results ‘’bosutinib could become a very welcome new treatment option for frontline therapy for CP CML.” In his discussion of this abstract, Daniel DeAngelo, MD, PhD (Dana-Farber Cancer Center, Boston, Massachusetts, United States), commented that patients with CML who achieve rapid responses have excellent long-term outcomes. Responses with second generation TKIs, including bosutinib are faster and deeper than with imatinib. Due to toxicity concerns and no survival benefit observed so far with these agents, imatinib remains a reasonable choice for the majority of patients. It is good to have choices in particularly for high risk patients said Dr DeAngelo, and bosutinib is a valuable addition to available frontline therapies for selected patients with CP CML.
High Response Rates With Ublituximab and Ibrutinib Combination in High-Risk CLL
Patients with chronic lymphocytic leukemia (CLL) and high-risk molecular features, such as 11q deletion, 17p deletion, or TP53 mutation, continue to have poor prognoses despite treatment with novel therapy, such as ibrutinib. Therefore, improving ibrutinib therapy, potentially through combinations with other agents, is a high priority. The open-label, phase III GENUINE study (Abstract 7504) randomized 126 previously treated high-risk patients with CLL to receive either the combination of ublituximab and ibrutinib or ibrutinib alone. Ublituximab, a novel anti-CD20 monoclonal antibody with enhanced antibody dependent cellular cytotoxicity (ADCC) activity, was given as a 900 mg infusion on days 1, 8, and 15 of cycle 1; day 1 of cycles 2 through 6; then every 3 cycles. Ibrutinib alone or in combination with ublituximab was given at the standard dose of 420 mg daily. Ublituximab plus ibrutinib was associated with an overall response rate of 78%, including a 7% CR, compared with 45% and 0% CR with ibrutinib monotherapy (P<.001). Patients receiving the combination achieved minimal residual disease negativity at a significantly higher rate than with monotherapy (19% vs 2%; P<.01). There was a trend toward improved progression-free survival in patients receiving the combination, but this was not statistically significant at the time of analysis (HR 0.559, P = .229). With the exception of infusion related reactions (54% all grades), the addition of ublituximab did not alter the safety profile of ibrutinib monotherapy. The discussant of this abstract, Nitin Jain, MD (MD Anderson Cancer Center, Houston, Texas, United States), said that while these early results are interesting, longer follow-up is required to determine the clinical relevance of this combination. He also pointed out that the type of anti-CD20 antibody best for use in combination with ibrutinib remains to be determined and that several studies evaluating this are ongoing.
For additional data across different hematologic malignancies, please see prIME Oncology’s Virtual Poster Session, prIME Downloadable Slides from the 2017 ASCO Annual Meeting, and prIME Clinical Updates from the 2017 international conference on malignant lymphoma in Lugano.