Patient Factors, Safety, and Long-Term Efficacy Best Inform Treatment Selection Across Hematologic Malignancies

Michael Choi, MD

With several recent approvals across hematologic malignancies and continued interest in building upon prior standard regimens to find new efficacious combinations, proper consideration of data on the long-term effects of treatment; agent toxicity profiles; and patient priorities, including convenience of administration and quality of life, will ensure successful incorporation of regimens into the ever-shifting treatment landscape, according to Michael Choi, MD.

“It’s exciting to see things that are changing the fundamental approach to diseases [such as] diffuse large B-cell lymphoma [DLBCL], which we’ve treated the same way for a few decades,” Choi said in an interview with OncLive^® regarding a recent OncLive State of the Science Summit™ on hematologic malignancies, which he chaired.

In the interview, Choi expanded on significant advancements and treatment considerations in hematologic malignancies that were discussed by his colleagues at the event. These included ongoing efforts to expand treatment options in chronic lymphocytic leukemia (CLL) beyond Bruton tyrosine kinase (BTK) inhibitor– or venetoclax (Venclexta)–based regimens, the significance of the FDA approval of momelotinib (Ojjaara) in myelofibrosis with anemia, the importance of patient input when considering frontline treatment with BTK inhibitors in mantle cell lymphoma (MCL), and the use of CAR T-cell therapy as a mainstay treatment strategy for DLBCL.

Choi, who is a hematologist/medical oncologist and associate professor of medicine at University of California San Diego (UCSD) Health, expanded further on advancements in CLL from his own presentation in another interview.

OncLive: What are therapeutic alternatives beyond BTK inhibitors or venetoclax with or without a CD20 monoclonal antibody for the frontline treatment of CLL, according to the presentation by Benjamin Heyman, MD?

Choi: Dr Heyman did a great job summarizing the current landscape and [discussing] how we have 2 highly effective options. It’s up to us to partner with our patients and their loved ones to decide which approach fits best with their priorities and preferences. The next question being answered as we speak is whether we can combine these 2 strategies: Can we use a BTK inhibitor with venetoclax and leave out the inconvenience and immune suppression associated with CD20 antibody infusions in the process?

There are trials occurring now to address that question. At UCSD, we’re involved in the [phase 3] MAJIC trial [NCT05057494] where patients with CLL or small lymphocytic lymphoma are randomly assigned to receive either acalabrutinib [Calquence] and venetoclax or venetoclax and obinutuzumab [Gazyva]. I’m enthusiastic and hopeful that [findings from] these trials are successful [so] patients have yet another option with advantages in convenience, safety, and efficacy.

Per the presentation by Amanda Kagan, MD, what are the implications of the FDA approval of momelotinib for patients with myelofibrosis?

Dr Kagan presented findings from the main trials that led to the approval [of] momelotinib for patients with myelofibrosis. As a physician, I’ve seen how challenging it can be to treat some patients with myelofibrosis who also have anemia. Anemia often initially worsens [with] other JAK inhibitors, and this can prevent some patients from tolerating the drug or effective doses of the drug. The approval of momelotinib is very important for patients who may be presenting with anemia, [whether they have anemia] before starting treatment or develop it as an adverse effect of other treatments. It will be interesting to see how this gets incorporated into our practices.

How could BTK inhibitors be incorporated into the frontline setting in MCL, based on the presentation by William B. Pearse, MD?

BTK inhibitors have shown great efficacy in patients with MCL, though perhaps the duration of remission has not been as long as we’ve observed for patients with CLL. Nonetheless, they’re a good treatment option, particularly for patients who may want to minimize the risks of chemotherapy-based regimens.

For each patient, [the selection of a BTK inhibitor] is still going to [require] a balancing of different priorities, and I have similar discussions with my patients who have CLL. BTK inhibitors [have a] good safety profile and a high level of convenience [due to an] ease of administration but may have some disadvantages as far as the long-term or ongoing administration of treatment. Some patients who receive [these agents] may prefer to receive a chemotherapy regimen instead because of the finite duration of treatment. We’ll [hopefully] see how the duration of remission compares over time.

Per the presentation by Paul Cheng, MD, PhD, what are some factors to consider when deciding to use CAR T-cell therapy for patients with DLBCL?

Dr Cheng brought a lot of firsthand experience with designing some of those CAR T-cell trials [into the discussion]. [He helped] run the phase 3 ZUMA-7 trial [NCT03391466], which has changed the treatment paradigm for patients with DLBCL. The main takeaways are that patients with relapsed DLBCL should be considered for CAR T-cell therapy. The data are quite clear that it’s a more effective strategy than autologous stem cell transplant. There may be some limitations in the time that it takes to prepare a patient for CAR T-cell therapy, as it may be longer for patients with very aggressive disease. Except for that subgroup, that would be my preference for patients with relapsed DLBCL.