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Adding venetoclax to ibrutinib in high-risk patients with chronic lymphocytic leukemia (CLL) who have been on ibrutinib for more than one year was very effective in helping patients reach undetectable measurable residual disease (uMRD).
The first interim analysis of the Phase 2 HOVON 158/Next Step Trial was conducted halfway through a 15-month course of treatment with ibrutinib and venetoclax. As compared to baseline, PET-CT scanning showed a decrease in metabolic activity in all but one patient. However, despite the decrease in metabolic activity and, in some cases, normal metabolic activity on PET-CT scans, several patients had persistently enlarged lymph nodes.
Targeted therapies have greatly improved survival outcomes for patients with chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL). For example, Ibrutinib is so effective at controlling CLL / SLL that the overall survival of patients treated with first-line ibrutinib is no different from that of the general population.
Patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) who achieved undetectable measurable (or minimal) residual disease (uMRD) after fixed-duration ibrutinib + venetoclax treatment continue to have excellent outcomes four years after stopping initial therapy. The results of this study suggest that if patients achieve uMRD remission, it is safe to stop treatment.
For patients with relapsed/refractory chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL), the response to combination ibrutinib plus venetoclax treatment in the first two months seems to predict who will have deep, sustained responses.
In this study, patients with IGHV unmutated chronic lymphocytic leukemia (CLL) responded better to combination ibrutinib + venetoclax than patients with IGHV mutated CLL and were more likely to achieve measurable residual disease (MRD) negativity in the peripheral blood and bone marrow.
Fixed duration combination therapy of obinutuzumab, ibrutinib, and venetoclax with treatment adjustment based on clinical response and results of measurable residual disease testing shows high efficacy and safety for the front-line treatment of chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL / SLL) patients with del (17p) or TP53 mutation offering exciting hope for what has been an unmet need for this group of patients with high-risk disease.
Dr. Sun was interviewed by Dr. Brian Koffman, a physician, CLL patient, and executive vice president and chief medical officer of CLL Society, at the ASH 2022 meeting in New Orleans. In the interview, she elaborates on the research results and recommendations on how patients can avoid cardiac issues while taking ibrutinib or other Bruton’s tyrosine kinase (BTK) inhibitors.
In this interview, our own Dr. Brian Koffman interviewed Dr. John Seymour, Director of the Department of Hematology at Peter MacCallum Cancer Centre & Royal Melbourne Hospital in Melbourne, Australia. They discussed the latest updates to the safety data from the ELEVATE R/R study, which was the first clinical trial to compare acalabrutinib and ibrutinib head-to-head.
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