Danielle M. Brander, MD, hematologic oncologist, hematologist, assistant professor of medicine, Hematologic Malignancies and Cellular Therapy, member, the Duke Cancer Institute, Duke Health, discusses the primary analysis of the phase 1/2 TRANSCEND CLL 004 trial (NCT03331198) in patients with relapsed/refractory chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL).

The single-arm, multicenter study evaluated the use of the CAR T-cell therapy lisocabtagene maraleucel (Breyanzi; liso-cel) in patients with CLL/SLL who have progressed on a BTK inhibitor as well as on a venetoclax (Venclexta)–based regimen. Findings from 2 dose levels in this study which have been previously presented, Brander notes. The primary analysis of this study was presented at the 2023 iwCLL Annual Meeting, Brander states, adding that a total of 49 patients who had both exposure to a BTK inhibitor and to venetoclax were evaluated. The primary end point was rate of complete response (CR) and CR with incomplete marrow count recovery (CRi), Brander says. The rate of CR/CRi was 18% (95% CI, 9%-32%; 

A key secondary end point evaluated in this study was the rate of undetectable minimal residual disease (MRD) in the blood, which was 63% (95% CI, 48%-77%). This occurred in a patient population that has previously been treated with, and progressed on, 2 of the most effective therapies, Brander emphasizes.

Responses have been observed in a subgroup of patients who have maintained long-term responses, she adds. Although these outcomes are primarily observed in patients who achieved undetectable MRD by the end of treatment, Brander continues. Investigators have observed response durations exceeding a year among patients with some residual disease. This is particularly significant for patients on this study, due to their heavily pretreated status. Brander adds. Moreover, patients do not typically undergo any treatments following the dose of CAR T-cell therapy, she concludes.

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Danielle M. Brander, MD, discusses the primary analysis of the phase 1/2 TRANSCEND CLL 004 trial in patients with relapsed/refractory chronic lymphocytic leukemia or small lymphocytic lymphoma.


Dr Brander on Findings From the TRANSCEND CLL 004 Trial in Relapsed/Refractory CLL/SLL

Danielle M. Brander, MD, assistant professor of medicine, Department of Medicine, Duke University School of Medicine, hematologic oncologist and hematologist (malignant), Duke Cancer Center, Duke Health, discusses the role of achieving minimal residual disease (MRD) negativity with venetoclax (Venclexta)-based regimens in chronic lymphocytic leukemia (CLL). 

Achieving MRD negativity is desirable and achievable in patients with high-risk CLL who require deep remissions, Brander says. Moreover, achieving MRD negativity is a goal of treatment with time-limited venetoclax-based regimens, including venetoclax plus obinutuzumab (Gazyva) for 12 months in newly diagnosed CLL or venetoclax plus rituximab (Rituxan) for 24 months in the relapsed/refractory setting.

With these regimens, data have suggested that patients who achieve MRD negativity by the end of treatment have prolonged progression-free survival and, potentially, overall survival, Brander explains.

As expected, investigational combination regimens of BTK inhibitors plus venetoclax or obinutuzumab appear to induce higher rates of MRD negativity, but at the expense of added toxicity to patients, Brander says. Although the data with these combinations are encouraging, it is important to consider the patient’s goal of therapy before selecting a potentially more toxic regimen with the hope of achieving MRD negativity, Brander concludes.

Danielle M. Brander, MD, discusses the role of achieving minimal residual disease negativity with venetoclax-based regimens in chronic lymphocytic leukemia.  



Dr. Brander on the Role of MRD Negativity With Venetoclax-Based Regimens in CLL 

Danielle Brander, MD, assistant professor of medicine, Duke Cancer Institute, discusses the treatment of patients with relapsed/refractory chronic lymphocytic leukemia (CLL).

Brander says there is debate about which patients with CLL will benefit from chemotherapy versus chemoimmunotherapy. The majority of patients in the relapsed/refractory setting are being transitioned to novel therapies. Currently, patients in the relapsed/refractory setting can receive ibrutinib (Imbruvica) if they did not receive it in the frontline setting, idelalisib (Zydelig) if they had more than 2 prior lines of therapy or are not eligible for other treatments, or venetoclax (Venclexta). In June 2018, venetoclax was granted a full approval by the FDA for the treatment of patients with CLL with or without 17p deletion, following at least 1 prior therapy.

There are multiple targeted inhibitors that are being tested in this population, as well. Clinical trials are investigating next-generation BTK inhibitors such as acalabrutinib (Calquence). In high-risk patients, acalabrutinib will be randomized versus ibrutinib in a phase III trial to evaluate differences in toxicity, Brander says.

Danielle Brander, MD, assistant professor of medicine, Duke Cancer Institute, discusses the treatment of patients with relapsed/refractory chronic lymphocytic leukemia.

Danielle Brander, MD

Articles

Dr Brander on Findings From the TRANSCEND CLL 004 Trial in Relapsed/Refractory CLL/SLL

Dr. Brander on the Role of MRD Negativity With Venetoclax-Based Regimens in CLL

Dr. Brander on the Treatment of Relapsed/Refractory CLL