Tafasitamab Demonstrates Positive Real-World PFS and OS in DLBCL

For patients with relapsed or refractory diffuse large B-cell lymphoma in the US, tafasitamab elicited promising real-world efficacy outcomes.

Tafasitamab-cxix (Monjuvi) was found to generate positive real-world efficacy outcomes like progression-free survival (PFS), overall survival (OS), and overall response rate (ORR) in patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) in data presented in a retrospective medical chart review at the 2024 American Society of Hematology Annual Meeting & Exposition (ASH).¹

At a median follow-up time of 14.7 months (range, 8.5-17.1) from tafasitamab initiation, the real-world progression-free survival (PFS) with tafasitamab was 11.3 months (95% CI, 9.8-13.6) in the overall population (n = 181), and the real-world overall survival (OS) was 24.8 months (95% CI, 17.8-not evaluable [NE]). The real-world overall response rate (ORR) to the agent was 73.5%, which comprised a complete response (CR) rate of 23.2% and a partial response (PR) rate of 50.3%. In the patients who achieved a real-world CR or PR with the agent (n = 133), the real-world duration of response (DOR) was 9.6 months (95% CI, 8.3-13.3).

A multivariable analysis showed that factors significantly linked with increased risk of progression included receiving the agent in the third to fifth line (n = 51) vs the second line (n = 130; HR, 1.79; 95% CI, 1.20-2.66; P = .004), having Ann Arbor stage III to IV disease (n = 169) vs stage I to II (n = 10; HR, 0.30; 95% CI, 0.10-0.95; P = .041), increasing Charlson Comorbidity Index scores (n = 181; HR, 1.43; 95% CI, 1.03-1.97; P = .033), and bulky (n = 36) vs non-bulky (n = 145) disease (HR, 1.96; 95% CI, 1.26-3.05; P = .003). To overcome violation of proportional hazards assumption caused by the variable of ECOG performance status, coefficients had been adjusted for status of 2 or higher vs under 2 through stratifying the model on performance status.

Moreover, a cox proportional hazards model showed that factors significantly associated with increased risk of mortality included receiving tafasitamab in the third to fifth line vs the second line (HR, 2.39; 95% CI, 1.46-3.93; P < .001), increasing age (HR, 1.06; 95% CI, 1.03-1.09; P < .001), ECOG performance status of 2 or higher (n = 86) vs below 2 (n = 95; HR, 3.57; 95% CI, 2.13-5.97; P < .001), and bulky vs non-bulky disease (HR, 2.22; 95% CI, 1.27-3.87; P = .005).

“The additional follow-up from the initial data collection allowed for a more robust evaluation of the real-world effectiveness of tafasitamab in patients with relapsed or refractory DLBCL, predominantly in the community practice setting,” lead study author Kim Saverno, PhD, of Incyte Corporation, in Wilmington, Delaware, said in a poster presentation of the data. “These results support a real-world clinical benefit for tafasitamab, with the greatest benefit observed when [the agent] was received in second vs later lines of therapy.”

The CD19-targeted immunotherapy, tafasitamab, was approved by the FDA in July 2020 for use in combination with lenalidomide (Revlimid) in adult patients with relapsed or refractory DLBCL not otherwise specified, including DLBCL arising from low-grade lymphoma, and who are not candidates to undergo autologous stem cell transplant.² To date, few studies have evaluated the agent in a US real-world setting, according to Saverno.¹ She added that data from a real-world study were previously shared, but had a limited follow-up time of 6.5 months, which “precluded robust evaluations of the clinical effectiveness” of the agent.³

For the current retrospective, multisite, medical chart review, 23 physicians from Cardinal Health’s Oncology Provider Extended Network abstracted data from 181 eligible patients’ medical records into electronic case report forms. Notably, 83% of these physicians practiced in the community.¹ For patients to be considered eligible for the analysis, they must have started treatment with tafasitamab with or without concomitant lenalidomide for relapsed/refractory disease on or following October 21, 2020; be at least 18 years old at the time treatment with the agent was started; and have undergone at least 4 months of follow-up since treatment started. Those who died during this 4-month interval were still permitted. If patients received the agent as part of an interventional clinical trial, they were excluded.

A total of 182 patients met the prespecified eligibility criteria; 1 patient who received tafasitamab only as bridge therapy to CAR T-cell therapy was excluded. As such, a total of 181 patients were included in the study; 144 of these patients were still alive at last follow-up of initial data collection which had occurred between February 22, 2023, and March 29, 2023. Of those patients, 137 patients had additional follow-up data available and underwent additional data collection between December 18, 2023, and January 31, 2024. A total of 106 patients were alive at last follow-up.

“Data collected at the two time points were merged and descriptive statistics were used to summarize the results,” Saverno explained. “Kaplan-Meier analyses were used to calculate time-to-event end points and multivariable Cox analyses were used to assess factors associated with real-world PFS and OS.”

In the 181 total patients, the median age at the time of tafasitamab initiation was 71.1 years (range, 65.0-75.5). Most patients were White (64.1%), and more than half of patients were male (56.4%). Regarding Ann Arbor stage at time of treatment initiation, 5.5% had stage I or II disease, 93.4% had stage III or IV disease; this information was unknown for 1.1% of patients. ECOG performance status at the time of treatment initiation was 0 to 1 for 52.5% of patients and 2 or higher for 47.5% of patients. Revised International Prognostic Index for Diffuse Large B-cell Lymphoma was 3 to 5 for 80.5% of patients and 1 to 2 for 19.5% of patients.

“Over 70% of patients received tafasitamab in the second line, and 71% of patients had discontinued tafasitamab at the last follow-up, mostly due to disease progression,” Saverno noted. “Over half of the patients were still alive at the last follow-up, and among the patients still alive, half [were] still receiving tafasitamab at the time of the most recent follow-up.”

Additional treatment outcome data showed that in those who received tafasitamab in the second line (n = 130), the real-world ORR was 78.5%; this was comprised of a CR rate of 27.7% and a PR rate of 50.8%. For this group, the stable disease (SD) rate was 8.5%, the progressive disease (PD) rate was also 8.5%, and 4.6% of patients did not have these data available. In the group of patients who received the immunotherapy in the third line (n = 43), the real-world ORR was 62.8%; this comprised a CR rate of 11.6% and a PR rate of 51.2%. In this subset, the SD and PD rates were 18.6% and 11.6%, respectively; 7.0% of patients did not have these data available.

In patients who experienced a real-world CR as a best response to tafasitamab (n = 42), the median real-world DOR was 19.2 months (95% CI, 8.8-NE). In those who achieved a real-world PR as a best response to the agent (n = 91), the median real-world DOR was 8.5 months (95% CI, 6.8-10.0).

“This study is impacted by limitations inherent to real-world studies, such as unobserved and missing data,” Saverno concluded. “The number of participating oncologists was small and thus may not reflect the treatment patterns of all US oncologists managing patients with DLBCL.”

Disclosures: Dr Saverno cited employment and stock ownership with Incyte Corporation.

References

1. Saverno K, Nastoupil L, Feinberg B, et al. Real-world effectiveness of tafasitamab (tafa) for the treatment of relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL) in the United States. Blood. 2024;144(suppl 1):2375. doi:10.1182/blood-2024-193264
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 AG. July 31, 2020. Accessed December 8, 2024. https://investor.incyte.com/news-releases/news-release-details/fda-approves-monjuvir-tafasitamab-cxix-combination-lenalidomide
3. Saverno K, Zimmerman Savill KM, Feinberg B, et al. Tafasitamab for the treatment of relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL) in the US real-world setting. Blood. 2023;142(suppl 1):265. doi:10.1182/blood-2023-173143