Novel Combination Therapy Shows Exciting Results in Chronic Lymphocytic Leukemia, Mantle Cell Lymphoma

A combination of cirmtuzumab plus Imbruvica (ibrutinib) could be beneficial in treating patients with mantle cell lymphoma (MCL) or chronic lymphocytic leukemia (CLL)/small cell leukemia (SLL), according to data from a phase 1b/2 study presented at the 2020 ASCO Virtual Scientific Program.

Cirmtuzumab works by inhibiting ROR1, an onco-embryonic tyrosine kinase receptor, that binds to the Wnt5a protein and increases the growth and survival of tumors.

“Cirmtuzumab is a humanized monoclonal antibody against the ROR1,” Dr. Hun Ju Lee, assistant professor of medicine in the department of Lymphoma and Myeloma at The University of Texas MD Anderson Cancer Center, said while presenting the findings.

“Preclinical studies have shown that cirmtuzumab has activity against neoplastic processes, and in combination with ibrutinib, has shown synergistic activity. We hypothesize that the combination of cirmtuzumab and ibrutinib will be highly active, will be able to offer a deeper complete remission compared to ibrutinib alone, with favorable safety profiles of both agents being retained.”

The first phase of the study focused on finding the proper dose of the drugs for the phase 2 trial, or the expansion cohort. Eligible patients had relapsed/refractory MCL or relapsed/refractory or treatment-naïve CLL/SLL with measurable disease and limited or no prior BTK-inhibitor treatment.

The researchers reported no unexpected side effects for the two-drug combination, and only minor side effects for cirmtuzumab alone, proving that the agent is safe. Additionally, the average progression-free survival (PFS) was 17.5 months for patients who received the combination.

Eighty-three percent of patients with MCL responded to the drug; 58% had a complete response (CR) and 25% had a partial response (PR). The median time to CR was 3.6 months in heavily pretreated patients — two of whom had bulky disease more than 5 cm.

All of the patients (100%) were free of disease progression at an average follow-up of 9.9 months, and more than 82% remain on the study. The majority of patients with CLL (88%) had a partial response. “All of the patients with CLL have benefited, with the majority of patients achieving a [partial response],” Lee said.

“In conclusion, we would like to let the audience know that cirmtuzumab and ibrutinib were very safe, with minimal toxicities that were noted in terms of grade 3,” Lee said. “But the significant overall response rate of 83% and a 58% complete remission rate were impressive.”

Looking ahead, Lee said that he is excited for phase 3 of the trial, which will have expanded patient enrollment.

“We will continue to study and expand our patient enrollment,” he said. “At this point, we would like to thank our patient population, and all our co-investigators for this exciting trial.”

Editor's note: This article was updated on June 8, 2020 with accurate data.