Epperla Elucidates on Excitement With Tafasitamab and Selinexor in DLBCL

Narendranath Epperla, MD, MS

The diffuse large B-cell lymphoma (DLBCL) arsenal has expanded with the recent addition of tafasitamab-cxix (Monjuvi), and determining the optimal sequence of therapies will be a critical component in achieving the best benefit possible for patients, according to Narendranath Epperla, MD, MS.

“In the field of hematologic malignancies, these are exciting times,” said Epperla. “A lot of changes are happening. The standard of care from years ago is not the same as of today, and 5 years from now, it will be completely different. Novel agents, immunotherapies, and cellular therapies have completely revolutionized the treatment [of these patients].”

Tafasitamab was examined in combination with lenalidomide (Revlimid) in patients with DLBCL as part of the phase 2 L-MIND study (NCT02399085).¹ After a median follow-up of 13.2 months, 60% of patients (n = 48 of 80) who received the combination regimen experienced an objective response (95% CI, 48%-71%). Among those who responded, 43% achieved a complete response (n = 34; 95% CI, 32%-54%) and 18% experienced a partial response (n = 14; 95% CI, 10%-28%).

In July 2020, the combination of tafasitamab and lenalidomide was FDA approved for use in adult patients with DLBCL, including those with DLBCL arising from a low-grade lymphoma and those who are ineligible for autologous stem cell transplant.² The regulatory decision was based on the results from L-MIND.

Beyond tafasitamab, options like selinexor (Xpovio) have emerged for the treatment of heavily pretreated patients in later-line settings. “This is an agent that needs to be at our disposal, especially for patients who have received many [prior] treatments,” noted Epperla. Bispecific antibodies and chimeric antigen receptor [CAR] T-cell therapies have also shown potential as alternative options in the relapsed/ refractory setting.

In an interview with OncLive® during a 2020 Institutional Perspectives in Cancer webinar on hematologic malignancies, Epperla, a hematologist specializing in the treatment of Hodgkin and non-Hodgkin lymphomas at The Ohio State University Comprehensive Cancer CenterJames, expanded on findings from the L-MIND trial in DLBCL, as well as the significance of selinexor and other options in the pipeline.

OncLive^®: What makes tafasitamab a unique option in DLBCL? How are you applying the data that were reported from the L-MIND trial to your practice?

Epperla: L-MIND was a single-arm, phase 2 study where patients received tafasitamab, an anti-CD19 monoclonal antibody, with lenalidomide, an immunomodulator. Tafasitamab is [given via] intravenous infusion, while lenalidomide is an oral chemotherapy drug. Tafasitamab is an interesting agent because it [mediates B-cell lysis through apoptosis and immune effector mechanism], including antibody-dependent cell-mediated cytotoxicity and antibody- dependent cellular phagocytosis. When combined with lenalidomide, [the combination has] synergistic activity [that results in] increased [antitumor] effect.

In a recent presentation, long-term follow-up [data from the trial were reported]. We asked ourselves: How did the patients do long term? How did those who received 1 prior line of therapy vs 2 prior lines of therapy do [with this approach]?

At 24 months of follow-up, the overall response rate [ORR] was around 53% in patients who received tafasitamab plus lenalidomide. When you break [responses] down by prior line of therapy, in patients who received 1 prior line, the ORR was pretty good, around 60%. However, when you look at patients who received 2 prior lines of therapy, the ORR was around 45%. Progression-free survival followed the same pattern. Overall, I would say that this is a very important agent that is available and at our disposal for treating patients with relapsed/refractory DLBCL.

One important thing to note is that in my clinical practice, I like to use tafasitamab plus lenalidomide earlier in relapse. Overall, I tend to use this [combination] in patients who received 1 prior line of therapy or, at the most, 2 prior lines.

Selinexor is another agent that has emerged for later-line treatment. Where does this option fit into your treatment sequence?

[It’s important to highlight] the SADAL study [NCT02227251], which examined selinexor in [patients with] relapsed/refractory DLBCL, given the FDA approval of tafasitamab/lenalidomide in relapsed/refractory disease. Selinexor is an important agent to be aware of; it’s an XPO1 inhibitor and it works in a unique way. Notably, patients who received selinexor in the clinical trial were heavily pretreated. I already mentioned that I prefer to use tafasitamab/lenalidomide [early on] in the relapsed setting; I like to use selinexor [later].

What are some other exciting areas of active investigation?

Stay tuned for [more on] bispecific antibodies; these are really important agents [that we now have] in the therapeutic armamentarium for large cell lymphoma. The big question is: How do we sequence [these therapies]? Also, how do we use CAR T-cell therapy and where do we use this approach? How do we use bispecifics and where do we use them? With all the novel agents in between, will we use them as definite therapies or as bridging therapies?

Would you like to add anything else regarding these emerging approaches?

As we learn more about novel agents and cellular therapies, we need to be extremely aware of the toxicities [that come with these approaches]. These are not the same effects that we are used to [seeing] with our conventional cytotoxic chemotherapies. These safety profiles are completely different, so we need to be extremely aware of them; [toxicities] can be acute, subacute, or even delayed. Stay tuned for what is coming up in the future because the standard of care will continue to change every year.

References

1. Salles G, Duell J, González Barca E, et al. Tafasitamab plus lenalidomide in relapsed or refractory diffuse large B-cell lymphoma (L-MIND): a multicentre, prospective, single-arm, phase 2 study. Lancet Oncol. 2020;21(7):P978-988. doi:10.1016/S1470-2045(20)30225-4
2. FDA approves Monjuvi (tafasitamab-cxix) in combination with lenalidomide for the treatment of adult patients With relapsed or refractory diffuse large B-cell lymphoma (DLBCL). News release. MorphoSys and Incyte. July 31, 2020. Accessed January 26, 2021. http://bwnews.pr/2MaLyqZ
3. Kalakonda N, Maerevoet M, Cavallo F, et al. Selinexor in patients with relapsed or refractory diffuse large B-cell lymphoma (SADAL): a single-arm, multinational, multicentre, open-label, phase 2 trial. Lancet Haematol. 2020;7(7):e511-e522. doi:10.1016/S2352-3026(20)330120-4