Kami J. Maddocks, MD, an associate professor of clinical internal medicine, Division of Hematology, The Ohio State University Comprehensive Cancer Center–James, discusses remaining challenges in treating patients with follicular lymphoma.

The biggest challenge right now is treating patients with follicular lymphoma who relapse early, or within 24 months of completing their initial therapy, says Maddocks. These patients have more aggressive disease and it is harder for them to achieve long-term responses and remissions. Ongoing trials are examining the best treatment approach for these patients to overcome this challenge.

Another challenge is when follicular lymphoma turns into aggressive lymphoma, says Maddocks. Outside of an allogeneic transplant, which is rarely done, this is an incurable disease; patients will need treatment for the rest of their lives. Finding effective, long-lasting, and tolerable approaches is the goal for this population, concludes Maddocks.

Videos

Kami J. Maddocks, MD, discusses remaining challenges in treating patients with follicular lymphoma.

Dr. Maddocks on Remaining Challenges in Follicular Lymphoma

Kami J. Maddocks, MD, an associate professor of clinical internal medicine, Division of Hematology, The Ohio State University Comprehensive Cancer Center–James, discusses unanswered questions with BTK inhibitors in B-cell malignancies.

Currently, BTK inhibitors are approved as single agents for the treatment of patients with various B-cell malignancies, including mantle cell lymphoma (MCL), chronic lymphocytic leukemia, Waldenström macroglobulinemia, and marginal zone lymphoma, Maddocks explains. Patients typically continue on BTK inhibitors indefinitely as long as they are responding to and tolerating the regimen. 

In diseases such as MCL, BTK inhibitors are reserved for the relapsed/refractory setting, Maddocks says. However, bringing these agents to the frontline setting, as well as combining them with other agents, may induce deeper remissions. 

Additionally, the question remains as to whether these agents can be given in a time-limited approach where patients may stop treatment 1 or 2 years after achieving a deep, minimal residual disease-negative remission, explains Maddocks. In turn, this could potentially decrease the long-term toxicity that is associated with BTK inhibition. 

If a patient does stop therapy and has a subsequent relapse, the question regarding the utility of retreatment with BTK inhibitors remains unanswered, says Maddocks. 

Kami J. Maddocks, MD, discusses unanswered questions with BTK inhibitors in B-cell malignancies.  



Dr. Maddocks on Unanswered Questions With BTK Inhibitors in B-Cell Malignancies 

Kami J. Maddocks, MD, an associate professor of clinical internal medicine, Division of Hematology, The Ohio State University Comprehensive Cancer Center–James, discusses the role of tazemetostat (Tazverik) in patients with 

Tazemetostat was recently approved by the FDA in June 2020 for adults with relapsed/refractory FL whose tumors are positive for an 

mutation as detected by an FDA-approved test and have received at least 2 prior systemic therapies, and adults with relapsed/refractory disease who have no satisfactory alternative treatment options, says Maddocks. 

The regulatory decision was based on data from 2 open-label, single-arm cohorts from the phase 1/2 E7438-G000-101 study, which showed more activity in patients with EZH2-mutated disease compared with those who had wild-type disease. However, responses were still observed in those with wild-type disease, adds Maddocks.

Tazemetostat provides patients with another oral therapy in this setting, says Maddocks. Overall, all the available therapies for patients with follicular lymphoma have toxicities, but it appears that tazemetostat may be better tolerated. As such, this is an option that could potentially be used earlier on in the treatment journey compared with other options, concludes Maddocks.

Kami J. Maddocks, MD, discusses the role of tazemetostat in patients with EZH2-mutant follicular lymphoma.


Dr. Maddocks on the Role of Tazemetostat in EZH2-Mutant Follicular Lymphoma

Kami J. Maddocks, MD, associate professor of clinical internal medicine, Division of Hematology, The Ohio State University Comprehensive Cancer Center–James, discusses emerging therapies in follicular lymphoma. 

As displayed in recent data, CAR T-cell therapy appears to be a promising treatment ​modality for patients with follicular lymphoma; however, some patients may benefit more from the therapy than others, says Maddocks. 

Moreover, bispecific antibodies and antibody​-drug conjugates have been studied in several lymphoma subtypes, ​including follicular lymphoma, ​Maddocks explains. Although these data are still in early stages, they suggest that the agents may result in less toxicity with easier administration.  

These emerging therapies continue to garner excitement in the field and could potentially emerge as treatment options in the future​, Maddocks concludes.

Kami J. Maddocks, MD, discusses emerging therapies in follicular lymphoma.

Dr. Maddocks on Emerging Therapies in Follicular Lymphoma 

Kami J. Maddocks, MD, associate professor of clinical internal medicine, Division of Hematology, The Ohio State University Comprehensive Cancer Center–James, discusses treatment considerations in follicular lymphoma. 

Patient factors, disease characteristics, and patient preference play a role in determining optimal treatment selection for a particular patient with follicular lymphoma, explains Maddocks. 

Disease bulk, disease-related symptoms, time-to-response, and the toxicity profile of the treatment also factor into the decision, Maddocks says. 

Additionally, patient preference should be considered as some patients prefer to avoid chemotherapy and explore time-limited therapy or oral therapy options instead, concludes Maddocks. 

Kami J. Maddocks, MD, discusses treatment considerations for treatment selection in follicular lymphoma.  


Dr. Maddocks on Treatment Considerations in Follicular Lymphoma 

Kami J. Maddocks, MD, associate professor of clinical internal medicine, Division of Hematology, The Ohio State University Comprehensive Cancer Center–James, discusses the role of zanubrutinib (Brukinsa) in B-cell malignancies.

Zanubrutinib has demonstrated efficacy in patients with high-risk relapsed/refractory chronic lymphocytic leukemia with 17p deletion, relapsed/refractory mantle cell lymphoma (MCL), and Waldenström macroglobulinemia, says Maddocks.

data from the randomized phase 3 ASPEN trial

 demonstrated higher complete response and very good partial response rates with zanubrutinib compared with ibrutinib (Imbruvica) in patients with Waldenström macroglobulinemia.

Although the trial did not meet its primary end point, zanubrutinib was associated with a significantly reduced rate of atrial fibrillation, hypertension, and major bleeding, explains Maddocks.

Although additional research is needed to determine whether the agent has improved clinical activity compared with ibrutinib, zanubrutinib offers patients with B-cell malignancies another therapeutic option with less toxicity, concludes Maddocks.

Kami J. Maddocks, MD, discusses the role of zanubrutinib in B-cell malignancies.



Kami J. Maddocks, MD

Articles

Dr. Maddocks on Remaining Challenges in Follicular Lymphoma

Dr. Maddocks on Unanswered Questions With BTK Inhibitors in B-Cell Malignancies

Dr. Maddocks on the Role of Tazemetostat in EZH2-Mutant Follicular Lymphoma

Dr. Maddocks on Emerging Therapies in Follicular Lymphoma

Dr. Maddocks on Treatment Considerations in Follicular Lymphoma

Dr. Maddocks on the Role of Zanubrutinib in B-Cell Malignancies