Cirmtuzumab Plus Imbruvica Led to Increased Response Rates in MCL and CLL

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Cirmtuzumab plus Imbruvica led to an 83.3% overall response rate, with 38.9% complete response and 44.4% partial response rate, in patients with mantle cell lymphoma and chronic lymphocytic leukemia.

Cirmtuzumab and Imbruvica (ibrutinib) led to high overall response rates (ORR) in patients with mantle cell lymphoma (MCL) or chronic lymphocytic leukemia (CLL), according to findings from a study presented during the 2021 ASCO Annual Meeting. The treatment regimen was also well tolerated with minimal extreme side effects.

“The majority of the patients demonstrated a significant reduction in tumor sizes,” lead study author Dr. Hun Ju Lee, assistant professor of medicine in the Department of Lymphoma & Myeloma at The University of Texas MD Anderson Cancer Center in Houston, said during the presentation.

ORR, defined as the percentage of patients who experience a decrease in measurable disease, for patients with MCL was 83.3% and was 91.1% for patients with CLL. The complete response rates (or the disappearance detectable cancer) were 38.9% and 14.7% for the MCL and CLL groups, respectively. Ultimately, 94.4% of patients with MCL and 100% of patients with CLL benefitted from the cirtuzumab/Imbruvica treatment regimen.

Because MCL and CLL are considered incurable, the study aimed to test the efficacy and safety of cirmtuzumab, which inhibits tumor promoting activity of onco-embryonic tyrosine kinase receptor ROR1 found in many solid and hematologic cancers, plus Imbruvica in patients with relapsed/refractory MCL or treatment naïve or relapsed/refractory CLL.

The study was performed in three parts with separate groups. Part one, for dose escalation; part two, for dose expansion; and part three, comparing cirmtuzumab plus Imbruvica with Imbruvica alone in patient with CLL.

Overall, 26 patients with refractory MCL (median age 66.5, 15.4% women) and 34 patients with treatment naïve or replapsed/refractory CLL (median age 68, 23.5% women) were enrolled in the study.

For part one, 12 patients with MCL were enrolled, and five into part two. The average number of prior regimens was two, including patients relapsing after Imbruvica (four patients), autologous stem-cell transplantation (three patients), autologous stem cell transplantation/allogenic stem cell transplantation (one patient) and autologous stem cell transplantation /CAR-T (one patient). For patients with CLL, at least 74% were high risk in parts one and two.

In part one, cirmtuzumab was given intravenously five times every two weeks, and then every four weeks. Researchers assessed the safety profile of cirmtuzumab during the first 28 days, which was then followed by Imbruvica at approved doses for each indication. A treatment regimen of cirmtuzumab (600 mg) given intravenously three times every two weeks, and then every four weeks, in combination with Imbruvica starting day zero, was chosen as the recommended dosing for parts two and three.

“The efficacy is robust in many of these pre-treated patients,” Lee said.

Side effects with 20% or greater incidence were: diarrhea (41%), contusion (39%), fatigue (39%), upper respiratory infection (31%), hypertension (25%), joint pain (23%). Regarding severe side effects, 13% of patients experienced neutropenia and 1% experienced thrombocytopenia.

“In summary, cirmtuzumab plus (Imbruvica) is a very well tolerated regimen,” Lee noted.

Of note, the phase 2 study for CLL is completed, and is awaiting a long-term follow-up. Phase 2 for MCL is currently enrolling.

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