Matthew S. Davids, MD, MMSc

Matthew S. Davids, MD, MMSc, an associate director with the Center for Chronic Lymphocytic Leukemia; director of clinical research, Lymphoma Program; and medical oncologist, Dana-Farber Cancer Institute and an assistant professor of medicine with Harvard Medical School, discusses the prognosis expected for patients with mantle cell lymphoma (MCL), as well as chronic lymphocytic leukemia (CLL), in the relapsed/refractory population.

The advent of the BTK inhibitor ibrutinib (Imbruvica) certainly improved the outlook for patients with relapsed/refractory MCL and CLL, Davids says. It is an active drug, but the durability of response is relatively short among those with high-risk disease. In MCL, for example, even though the response rates are high, the progression-free survival is only a little over 1 year with ibrutinib as monotherapy.

This serves as the rationale for the development of combination approaches for this patient population, and there are a number in development now, says Davids. One combination is looking at dual blockade of the B-cell receptor pathway. It is known the CLL cells and MCL cells depend heavily on this pathway, and there is another arm of the pathway that has Pi3K as a key node, so there is interest in going after this other arm of the pathway to potentially prevent resistance to ibrutinib as a monotherapy, Davids concludes.

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Matthew Davids, MD, MMSc, discusses the prognosis expected for patients with mantle cell lymphoma, as well as chronic lymphocytic leukemia, in the relapsed/refractory population.

Using Combination Therapy for Patients With Relapsed/Refractory MCL

Matthew S. Davids, MD, MMSc, director of clinical research in the Lymphoma Program and a medical oncologist at Dana-Farber Cancer Institute, as well as an assistant professor of medicine at Harvard Medical School, discusses the current treatment landscape for patients with chronic lymphocytic leukemia (CLL) beyond chemoimmunotherapy.

According to Davids, a number of novel agents have been approved by the FDA for the treatment of patients in the frontline setting, which is beginning to replace the role of chemoimmunotherapy in this space. The most widely used treatment for frontline CLL has become ibrutinib (Imbruvica), which is a Bruton’s kinase (BTK) inhibitor.

The second BTK inhibitor, acalabrutinib (Calquence) received its approval for the frontline treatment of patients with CLL. Both BTK inhibitors are continuous therapy regimens, but the combination of venetoclax (Venclexta) plus obinutuzumab (Gazyva) is now challenging this approach as a time-limited therapy regimen to replace chemoimmunotherapy.

Matthew S. Davids, MD, MMSc, discusses the current treatment landscape for patients with chronic lymphocytic leukemia beyond chemoimmunotherapy.

Novel Agents Could Improve Chemoimmunotherapy in Chronic Lymphocytic Leukemia

Matthew Davids, MD, MMSc, an associate director with the Center for Chronic Lymphocytic Leukemia; director of clinical research, Lymphoma Program; and medical oncologist, Dana-Farber Cancer Institute and an assistant professor of medicine with Harvard Medical School, discusses the longer-term follow-up data from the phase 3 UNITY-CLL clinical trial, which evaluated umbralisib (TGR-1202) in combination with ibrutinib (Imbruvica) as treatment of patients with chronic lymphocytic leukemia (CLL).

The results, which were presented during the 2020 European Hematology Association Congress, demonstrated that complete responses increased overtime, showing that the initial results observed in the study were holding up for patients with CLL. These patients are having really good durability of these responses, says Davids. There were also higher rates of complete remission that investigators expected for the combination compared with ibrutinib on its own.

Davids says that there is an argument in the field about whether complete remission matters in patients who are on a continuous therapy, but he believes the data are supportive of the possibility that getting into deeper remissions can sustain remissions longer, as what’s been observed in the impressive progression-free survival and overall survival data. However, longer-term follow-up is needed to know for certain, as well as comparative studies to answer that question more definitively.

<< View more from the phase 3 UNITY-CLL study

Matthew Davids, MD, MMSc, discusses the longer-term follow-up data from the phase 3 UNITY-CLL clinical trial, which evaluated umbralisib in combination with ibrutinib as treatment of patients with chronic lymphocytic leukemia.

Ibrutinib Plus Umbralisib Induce Survival Benefit in Patients With CLL

Matthew S. Davids, MD, MMSc, associate director, Center for Chronic Lymphocytic Leukemia, Dana-Farber Cancer Institute, and assistant professor of medicine, Harvard Medical School, discusses the significance of the findings from TRANSCEND CLL 004, a phase I/II trial investigating the chimeric antigen receptor (CAR) T-cell therapy lisocabtagene maraleucel (liso-cel; JCAR017) in patients with relapsed or refractory chronic lymphocytic leukemia (CLL).

All patients were post-ibrutinib (Imbruvica), and many of the patients were also post-venetoclax (Venclexta). According to Davids, this is a very refractory patient population with CLL. Overall, 45% of patients achieved a complete remission while about three-quarters of the patients achieved minimal residual disease undetectability when treated with liso-cel.

More severe adverse events, such as cytokine release syndrome or neurologic events in particular, were observed less frequently with liso-cel as compared to other CAR products that have been tested in this patient population.

Matthew S. Davids, MD, MMSc, discusses the significance of the findings from TRANSCEND CLL 004, a phase I/II trial investigating the CAR T-cell therapy lisocabtagene maraleucel in patients with relapsed or refractory chronic lymphocytic leukemia.

Matthew S. Davids, MD, MMSc | Authors

Articles

Using Combination Therapy for Patients With Relapsed/Refractory MCL

Novel Agents Could Improve Chemoimmunotherapy in Chronic Lymphocytic Leukemia

Ibrutinib Plus Umbralisib Induce Survival Benefit in Patients With CLL

Exploring Durable Responses With Liso-Cel for Relapsed/Refractory CLL