NCCN Guidelines Grant Tafasitamab Category 2A Designation in DLBCL

Tafasitamab-cxix (Monjuvi) has been added to the Clinical Practice Guidelines in Oncology by the National Comprehensive Cancer Network (NCCN) for the treatment of patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL) who are not candidates for autologous stem cell transplant (ASCT), according to a press release from MorphoSys AG.¹

Specifically, the NCCN Guidelines now include the combination of tafasitamab and lenalidomide (Revlimid) with a Category 2A designation for the treatment of adult patients with relapsed/refractory DLBCL not otherwise specified (NOS), including DLBCL arising from low-grade lymphoma who are ineligible for ASCT.

“We are very gratified the NCCN acted quickly to include Monjuvi in combination with lenalidomide with a Category 2A designation in its Clinical Practice Guidelines in Oncology as a treatment for patients with relapsed or refractory DLBCL who are not candidates for transplant,” Malte Peters, MD, chief research & development officer of MorphoSys, stated in the press release.

On July 31, 2020, the FDA granted an accelerated approval to tafasitamab in combination with lenalidomide for the treatment of adult patients with relapsed or refractory DLBCL NOS, including DLBCL arising from low-grade lymphoma, and who are not eligible for autologous stem cell transplant.²

“This targeted therapeutic option helps address an immediate medical need for patients who previously had limited treatment options,” said Peters. “There is no other FDA-approved second line treatment for these patients with a 2A designation within the NCCN guidelines.”

The humanized Fc-modified cytolytic CD19-targeting monoclonal antibody was granted accelerated approval based on overall response rate (ORR) data from the phase 2 L-MIND trial. The regulatory decision marks the first approval of a second-line therapy for adult patients who had progressed during or after first-line treatment. Continued approval of the agent will be dependent on verification in confirmatory trials.

In L-MIND, the combination of tafasitamab and lenalidomide led to an ORR of 55%, consisting of a 37% complete response (CR) rate and an 18% partial response (PR) rate. The median duration of response (DOR) was 21.7 months.³

In the open-label, multicenter, single-arm trial, investigators evaluated the combination in patients with relapsed/refractory DLBCL who had received 2 or fewer prior lines of therapy, including an anti-CD20 agent, who were not considered to be candidates for high-dose chemotherapy and subsequent autologous stem cell transplant.

ORR served as the primary end point of the trial. Key secondary end points included DOR, progression-free survival (PFS), and overall survival (OS). At the November 30, 2018 cutoff date, 80 patients had enrolled on the trial and had received the combination. All patients had been followed for at least 1 year.

A prior update that was presented during the 2019 ASCO Annual Meeting demonstrated that the combination demonstrated promising activity across most patient subgroups, including those who were refractory to prior treatments. The median time to response was 1.8 months, and the median time to a CR was 3.4 months. The median DOR had not yet been reached, but the 12-month DOR rate for those who had achieved a CR was 87%.

Moreover, the investigator-assessed ORR was 58% in the intent-to-treat population, with a CR rate of 33% and a PR rate of 25%. Fifteen percent of patients achieved stable disease, while 19% had progressive disease. Nine percent of patients were determined to be unevaluable. The 12-month DOR in this population was 70.1% versus 87%.0 in patients who achieved a CR.

Regarding safety, the Warnings and Precautions for tafasitamab include infusion-related reactions (6%), serious or severe myelosuppression, including neutropenia (50%), thrombocytopenia (18%), anemia (7%), infections (73%), and embryo-fetal toxicity. Additionally, 3.7% of patients discontinued treatment because of neutropenia.

Moreover, the most commonly reported adverse reactions included neutropenia, fatigue, anemia, diarrhea, thrombocytopenia, cough, pyrexia, peripheral edema, respiratory tract infection, and a decrease in appetite.

“The inclusion of Monjuvi in the NCCN Guidelines will help further inform healthcare providers of this advancement for patients,” Peg Squier, MD, Group Vice President, US Medical Affairs, Incyte, said in the press release. “We believe Monjuvi has the potential to address an urgent medical need for patients with relapsed or refractory DLBCL and are pleased that the NCCN has acknowledged the clinical benefit of this targeted therapeutic option.”

Currently, a marketing authorization application being reviewed for the approval of tafasitamab plus lenalidomide in the European Union has been validated by the European Medicines Agency. The application is currently under review for the treatment of adult patients with relapsed/refractory DLBCL, including DLBCL arising from low-grade lymphoma, who are not eligible for ASCT.

References

1. National Comprehensive Cancer Network® adds Monjuvi® (tafasitamab-cxix) to its clinical practice guidelines in oncology for B-cell lymphomas. August 18, 2020. Accessed August 20, 2020. bit.ly/3l2Kt1b
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 August 20, 2020. https://bwnews.pr/3jZhE5g
3. Maddocks KJ, Duell J, Barca EG, et al. Update of the single-arm phase II L-MIND study of MOR208 + lenalidomide (LEN) in relapsed/refractory diffuse large B-cell lymphoma (R-R DLBCL): Response rates in patient subgroups with poor prognosis. J Clin Oncol. 2019;37(suppl 15):7521. doi:10.1200/JCO.2019.37.15_suppl.7521