Novel Drug Plus Rituxan May Serve as ‘New Treatment Option’ for Relapsed/Refractory Lymphoma Subset

While CAR-T cell therapy and stem cell transplant have drastically changed the outcomes for patients with B-cell lymphomas, some patients are not eligible for these potentially curative options, leaving much to be desired by way of improving outcomes for these patients.

Now, data presented at the 2021 ASH Meeting and Exposition may lead to a treatment option that may improve outcomes in this patient population.

“Patients with (diffuse large B-cell lymphoma [DLBCL]) are treated with curative intent and oftentimes are cured. However, not all patients are cured, and patients with relapsed/refractory non-Hodgkin lymphoma and particularly aggressive lymphomas like DLBCL who are not candidates for stem cell transplant or CAR-T cell therapy have a particularly poor prognosis and there’s clearly a medical need for new treatment options,” study author Dr. Moshe Y. Levy, a hematologist at Baylor Scott & White Charles A. Sammons Cancer Center in Dallas, said when presenting the data.

Researchers analyzed the safety and efficacy of a new drug called naratuximab emtansine — plus Rituxan (rituximab) — in patients with pretreated relapsed/refractory DLBCL and other non-Hodgkin B-cell lymphomas (B-NHL) who are not eligible for stem cell transplant.

Part one of the study was a safety run-in followed by expansion, where patients received 0.7 mg/kg of naratuximab emtansine (an antibody drug conjugate) plus 375 mg/m2 of Rituxan every three weeks (Q3W).

Then, part two of the study comprised 66 patients with relapsed/refractory DLBCL. Patients in this portion of the study were assigned to either group A, which was the Q3W regimen (33 patients) or group B, where participants received 0.4, 0.2, and 0.2 mg/kg of naratuximab emtansine on days one, eight, and 15 of a 21-day cycle plus 375mg/m2 of Rituxan on day 1 (30 patients). Patients underwent six cycles of treatment with the option for extension.

“This study did include a lot of patients who are often excluded from DLBCL trials, and the inclusion criteria here were quite broad and very consistent with patients we routinely see in our clinic,” Levy said.

The main goal of the study was to determine the percentage of patients whose cancer shrunk as a result of treatment — known as overall response rate (ORR). Researchers also assessed how the drugs worked and quality of life, which was measured by the FACTLym quality of life questionnaire — a health assessment measuring various types of well-being.

The ORR in the efficacy evaluable patients with DLBCL was 44.7%, which included 24 patients (31.6%) who experienced a complete response (CR) and 10 (13.2%) partial responses (PR). Nine patients (11.8%) had stable disease (SD) and 33 (43.4%) had progressive disease (PD).

In part one, 16 patients with DLBCL were efficacy evaluable: six were primary refractory and 10 were refractory to the last line of therapy. In this group, the ORR was 25%.

There were 30 efficacy evaluable patients in each of groups A and B in part two of the study. Each group had an ORR of 50%, with 43.3% and 33.3% CR in groups A and B, respectively. Median duration of response (DOR) in the DLBCL patients was not reached, and median duration of follow-up in patients who responded was 15 months.

For patients with follicular lymphoma, the ORR was 57%, including five CRs, three PRs, three SDs and three PD. At a mediation follow-up of 21.8 months, average DOR was not reached. In patients with mantle cell lymphoma, four of the six were efficacy evaluable. Two patients had CR and two had PD.

Regarding quality of life, patients with DLBCL in groups A and B whose disease responded to treatment reported a clinically meaningful improvement of three points on the lymphoma subscale of the FACT-Lym QoL.

“Change from baseline until the last assessment up and including the treatment was assessed in both responders and non-responders. On this index, 38% of responders had a clinically important improvement of at least seven points, versus only 8% of non-responders,” Levy said. “So we concluded that the treatment was associated with a significant increase in well-being in 38% of responders.”

The most common severe side effects were hematologic events (those relating to blood), though Levy said that they were overall manageable and not as consequential. The most common side effect was neutropenia (54%), which included 5% pneumonia or lung infection and febrile neutropenia in 4%. Eight patients discontinued therapy because of side effects, and of the 10 deaths, only two were considered to be related to treatment. There were three serious or severe liver-related side effects, and two cases of non-serious neuropathy that was stage 3 or higher.

“Naratuximab (emtansine) plus Rituxan can certainly represent a new treatment option for relapsed/refractory non-Hodgkin lymphoma, especially relapsed/refractory DLBCL, which is still a particularly unmet need for folks not candidates for potentially curative therapy with CAR T or high-dose chemotherapy and autologous stem cell rescue,” Levy said. “Furthermore, the (side effect) profile as well as efficacy of this treatment lends itself quite well to additional combinations to be explored.”

A version of this article was originally published on OncLive as, “Naratuximab Emtansine Plus Rituximab Serves Unmet Need in Relapsed/Refractory DLBCL Treatment.”

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