Lymphoma Advances Include Pivotal Trials, Novel Agents, and Effective Combos

Sunita D. Nasta, MD

Treatments for patients with follicular lymphoma, diffuse large B-cell lymphoma (DLBCL), and T-cell lymphoma have been evolving with clinical data of novel single-agent and combination approaches, said Sunita Nasta, MD.

For example, in T-cell lymphoma, the randomized ECHELON-2 trial looked at brentuximab vedotin (Adcetris) with cyclophosphamide, doxorubicin, and prednisone (CHP) versus CHP plus vincristine (CHOP) for patients with CD30-positive peripheral T-cell lymphoma. Results showed a median progression-free survival (PFS) of 48.2 months with brentuximab vedotin plus CHP compared with 20.8 months with conventional CHOP (HR, 0.71; 95% CI, 0.54-0.93; P = .0110).

“[This combination] should be one of the major considerations for upfront therapy for this patient population,” Nasta said. “About 50% of all peripheral T-cell lymphomas have some expression of CD30 and in anaplastic large T-cell lymphoma, the majority of patients are CD30 positive.”

In an interview during the 2019 OncLive^® State of the Science Summit™ on Hematologic Malignancies, Nasta, associate professor of clinical medicine and chair of the Clinical Trials Review Monitoring Committee, Penn Medicine, discussed these exciting updates in follicular lymphoma, DLBCL, and T-cell lymphoma and the impact they will have on the upfront and relapsed/refractory paradigms.

OncLive: Could you discuss some recent advances in specific types of lymphoma?

Nasta: Follicular lymphoma is an indolent or low-grade lymphoma. The exciting findings inside follicular lymphoma research over the last year have been the use of new small molecules, as well as combinations with immunomodulatory agents, such as lenalidomide (Revlimid).

Diffuse large B-cell lymphoma is still an unmet need. There are results of using two very interesting trial agents in combination, both in the relapsed setting and in the frontline setting.

Finally, in T-cell lymphoma, there are the results of the ECHELON-2 trial, which will be one frontline option for patients with T-cell lymphoma. Also, there are some interesting new salvage options for patients with peripheral T-cell lymphoma.

Starting with follicular lymphoma, what updates are particularly exciting?

The approaches to both frontline and relapsed/refractory follicular lymphoma using antibody therapy in combination with lenalidomide [are intriguing]. There are results of the [AUGMENT and RELEVANCE] trials and the GALEN trial, as well as new options for relapsed therapy with lenalidomide.

I also discussed two new PI3K inhibitors: copanlisib (Aliqopa) and duvelisib (Copiktra), the latter of which is [highlighted in] the DYNAMO trial of relapsed/refractory follicular lymphoma.

How will these new options change the space of follicular lymphoma?

I don't think lenalidomide will necessarily change the space, but now we have the data to justify what we have been doing in an investigational setting.

In terms of new drugs, the PI3K inhibitors provide options that were previously much more toxic. Now, PI3K inhibitors can provide a way to manage the disease with a relatively low toxicity burden and good overall response rates.

There are unmet needs in DLBCL. Could you expand on the steps being taken to address them?

In general, people think of large cell lymphoma as a highly curable malignancy, and two-thirds of patients who are treated with R-CHOP have long-term, complete remissions.

However, for those patients who relapse, we are left with significant unmet needs. Only about 10% will have long-term complete remission with the current salvage of autologous stem cell transplant.

There is a new antibody approach using polatuzumab vedotin (Polivy), which is an anti-CD79b agent in combination with R-CHOP in the frontline setting, and bendamustine/rituximab (Rituxan) in the second-line setting. That may provide options for patients who are either not candidates for transplant or would not be able to tolerate CAR T-cell therapy.

Moving to T-cell lymphoma, what did the ECHELON-2 trial demonstrate? What impact do these data have on the T-cell lymphoma space?

The ECHELON-2 trial is a follow-up trial to ECHELON-1, which [explored] a frontline therapy for Hodgkin lymphoma. [ECHELON-2] added brentuximab vedotin to upfront therapy for patients with peripheral T-cell lymphoma.

This trial combined brentuximab vedotin with the backbone of CHOP without vincristine (CHP). The results do show that in comparison to CHOP therapy, brentuximab vedotin plus CHP is superior in terms of producing complete remission and long-term PFS.

Over the last 30 years in terms of salvage therapies, we have learned that single agents in the relapsed setting produce responses of about 25% to 30%, regardless of what we use.

Therefore, the real purpose of newer investigations is to see if combinations may be worthwhile. In particular, one combination that was reported by [Steven M. Horwitz, MD, of Memorial Sloan Kettering Cancer Center] looked at romidepsin (Istodax) in combination with duvelisib. It was found to have a significantly higher rate of response with decreased toxicities in comparison to either agent alone.

Horwitz S, O’Connor OA, Pro B, et al., Brentuximab vedotin with chemotherapy for CD30-positive peripheral T-cell lymphoma (ECHELON-2): a global, double-blind, randomized, phase 3 trial. Lancet. 2018;393(10168):229-240. doi: 10.1016/S0140-6736(18)32984-2.