Perseverance Underscores Success in Rare Lymphoma Research

Exhibiting perseverance in pursuing research for rare lymphoma subtypes has demonstrated success in attaining funding for highly specific trials, according to Andrew D. Zelenetz, MD, PhD.

In an interview with CancerNetwork®, Zelenetz, medical director of Quality Informatics at Memorial Sloan Kettering Cancer Center, discussed the state of rare lymphoma research relating to funding for highly specific investigations, particularly among lymphoma subtypes that may not have a large market.

Zelenetz began by suggesting that sponsors may not be interested in rarer lymphomas due to the limited number of cases that might otherwise inform treatment efficacy outcomes. Furthermore, he explained that although sponsors may be interested in funding variants of more common lymphomas, persistence on the part of the oncologist may help to attain funding for rare lymphoma research.

Highlighting an example from the phase 2 BOVen study (NCT03824483), he expressed that Anita Kumar, MD, a lymphoma specialist at Memorial Sloan Kettering Cancer Center, was attempting to assess a regimen similar to one that was initially assessed in chronic lymphocytic leukemia (CLL)––zanubrutinib (Brukinsa), obinutuzumab (Gazyva), and venetoclax (Venclexta; BOVen)––but for patients with mantle cell lymphoma (MCL). Initially unsuccessful, Zelenetz expressed that in highlighting the efficacy of the BOVen regimen in patients with CLL, the sponsor was ultimately willing to allocate funding for the MCL trial.

Zelenetz then explained that the trial itself evaluated P53-mutant MCL after prior research showed that efficacy outcomes with frontline chemo-immunotherapy for patients with P53-mutant MCL were worse than among other patient subgroups. He concluded by pointing to the success of the trial, which showed enhanced efficacy outcomes among patients with P53-mutant MCL following treatment with the BOVen regimen.

Transcript:

We want to do highly specific trials but sometimes, sponsors just are not interested. If you have a tiny market, it may not be great to develop drugs in that market, or [if] you have a certain amount of dollars….Even if you are willing to spend money on investigator-initiated trials, maybe you want the investigator-initiated trials in some variants of the more common lymphomas, rather than these rare lymphomas. Sometimes, it just takes perseverance. [Sometimes you must be] an annoying investigator and say, “You have to study this thing.”

A good example is a study for CLL, which we call the [phase 2] BOVen study. It [assessed] a combination of zanubrutinib plus obinutuzumab and venetoclax, and this was originally a CLL trial. One of my colleagues, Anita Kumar, MD, was trying to develop a 3-drug combination, similar to BOVen, with a competing BTK inhibitor, but could not get traction with the sponsor. I had an open trial, and I went, hat in hand, to the sponsor, and I said, “Well, look how good it is in CLL. [MCL is like CLL], why don’t we try it?”

Not only did we treat a rare disease; we treated a rare subpopulation of a rare disease, only P53-mutant. Why? Because that was a group where we had done well with chemo-immunotherapy in first-line [therapy] for most patients with MCL, [but] patients who had P53 mutations [experienced poor outcomes] with conventional chemo-immunotherapy. We were able to convince the sponsor to let us do a cohort of P53-mutant [disease], [and it] turned out to be quite successful. Sometimes, it takes a lot of perseverance.

Reference

Kumar A, Soumerai J, Abramson JS, et al. Zanubrutinib, obinutuzumab, and venetoclax for first-line treatment of mantle cell lymphoma with a TP53 mutation. Blood. 2025;145(5):497-507. doi:10.1182/blood.2024025563