Triple-Drug Combination for Relapsed and Refractory CLL

Combination treatments for relapsed chronic lymphocytic leukemia (CLL) may provide deeper and longer disease remissions and allow patients to stop treatment. Two new drugs, umbralisib and ublituximab, are being studied in this way. Combining these drugs with venetoclax may be effective and better tolerated. In this trial, patients with relapsed and refractory CLL received 3 28-day cycles of umbralisib (given daily) along with ublituximab, given once during cycles 1, 2, and 3. This was followed by umbralisib plus venetoclax for 9 additional cycles.

To date, 27 patients have been treated with the 3-drug combination of umbralisib and ublituximab plus venetoclax (UUV): 9 in the first phase of the study, and 18 in the second phase. The median age of these patients was 65 years. They had received a median of 2 prior therapies. Of 9 patients who had received prior ibrutinib, 4 were refractory. High-risk genetic features were found in most patients; examples include unmutated-IGHV genes, del17p or del11q, and TP53 mutation.

Among all patients with relapsed and refractory CLL who have been treated with UUV to date, the most common side effects were infusion reactions, low white blood-cell counts, anemia, elevated liver enzymes, fatigue, nausea, and diarrhea. Severe side effects included low counts of a certain type of white blood cells, infusion reactions, and blood clots. One patient discontinued study treatment due to a severe rash.

Among evaluable patients with relapsed and refractory CLL, the overall response rate associated with UUV was 100% after cycle 7. Of the 9 patients who finished 12 cycles of therapy, lymph node disease shrunk by a median of 87%, resulting in 4 complete responses and 5 partial responses. Seven patients have undetectable minimal residual disease in both blood and bone marrow. These patients have stopped therapy. With a median follow-up of 6 months, none of these patients has experienced progression of their CLL.

Researchers concluded that UUV shows good tolerability in patients with relapsed and refractory CLL. Preliminary results suggest that this chemotherapy-free regimen can result in undetectable minimal residual disease after 12 cycles, making it an effective treatment option. Ongoing studies are focused on patients with CLL who have relapsed after receiving a Bruton tyrosine kinase inhibitor. A multicenter trial will further explore use of the time-limited UUV regimen.

Abstract 360. ASH 2019.

Related Items

Conference Correspondent Coverage is Brought to You by the Publishers of:
CONQUER: the patient voice

Learn more about our family of publications.

View Our Publications