Jennifer L. Crombie, MD, on DLBCL: Real-World Outcomes With Novel Therapies in Relapsed or Refractory Disease

Jennifer L. Crombie, MD: We know that the treatment landscape of diffuse large B-cell lymphoma or DLBCL has significantly evolved over the past few years since the availability of multiple new therapeutic options that are now FDA approved for this disease. The outcomes of patients in the real world setting utilizing these novel agents, however, remains less clearly described. In our study, we utilize the CODA Electronic Health records database, which consists of patient demographic and clinical information from both academic and community practice sites across the United States. We identified over 5,700 patients with a diagnosis of DLBCL in the database. And further within this cohort, we identified 175 patients with relapsed refractory disease, who had been treated with a novel therapy. Novel therapies consisted of chimeric antigen receptor T-cell therapy, or CAR-T therapy, Tafasitamab plus Lenalidomide, Polatuzumab plus Bendamustine and Rituximab, and along Cetuximab, there were no patients in the database treated with Selinexor. Patients were also required to have at least one post index response assessment or date of death recorded following their treatment with the novel therapy. Patients were further classified as having received two or more versus three or more lines of therapy. We next examined outcomes within each treatment group. We found that outcomes were best among the patients treated with CAR T-cell therapy with overall response rates of approximately 75% and a median overall survival of 27 in 18 months, in patients who had received two or greater versus three or later lines of therapy. Outcomes were poorer among patients who had received other novel therapies. Those patients treated with Polatuzumab based regimens had an overall response of approximately 60% and a median overall survival of 7.5 months. And patients treated with Tafasitamab based regimens had response rates ranging from 35 to 40% depending on the line of therapy and a median overall survival of approximately six months. Patients treated with novel therapies after CAR T-cell had a particularly poor outcomes with overall survivals of less than three months. While it's encouraging that novel therapies are now available for patients with relapse or refractory DLBCL, our data highlight the persistent poor outcomes that are seen in the relapsed refractory setting, particularly after CAR-T relapse and the urgent need for ongoing treatment options in this space. Thankfully, other drugs including CD20, CD3 bispecific antibodies, as well as other novel therapies and combinations are being studied in ongoing clinical trials.