Treatment of Relapsed or Refractory Diffuse Large B-Cell Lymphoma: New Approved Options

Abstract

Overall, around 40% of patients with diffuse large B-cell lymphoma (DLBCL) have refractory disease or relapse after the first line of treatment. Until relatively recently, the prognosis of patients with relapsed or refractory DLBCL was very poor and treatment options were very limited. In recent years, several novel therapies have been approved that provide more effective options than conventional chemotherapy and that have manageable toxicity profiles. CAR-T cell therapy has become the new standard treatment for patients with refractory or early relapsed DLBCL, based on the positive results of the phase 3 ZUMA-7 and TRANSFORM clinical trials. This review addresses the role of CAR-T therapy and autologous stem cell transplantation in the treatment of these patients and other approved options for patients who are not candidates for transplant, such as the combinations of polatuzumab vedotin with bendamustine and rituximab, and tafasitamab with lenalidomide.

Keywords: CAR-T cell therapy; autologous stem cell transplantation; diffuse large-B cell lymphoma; polatuzumab vedotin; relapsed or refractory DLBCL; tafasitamab.

Figure 1

Proposed algorithm for the second-line treatment of DLBCL. ASCT, autologous stem cell transplantation; axi-cel, axicabtagene ciloleucel; DLBCL, diffuse large B-cell lymphoma; liso-cel, lisocabtagene maraleucel; pola-BR, polatuzumab-vedotin with bendamustine and rituximab; R-GemOx, rituximab, gemcitabine, and oxaliplatin; tafa-len, tafasitamab and lenalidomide. ¹ During the first year following the completion of first-line treatment. ² The selection of treatment (axi-cel or liso-cel) must be individualized based on CAR-T availability and the patient’s characteristics. Liso-cel could be favored in older patients or patients with organ dysfunctions [41]. ³ The selection of treatment must be individualized. In countries where CAR-T cell therapy is available in the third, but not the second line, the administration of bendamustine should be avoided in these high-risk patients due to its prolonged lymphodepletive effect [62]. Tafasitamab should also be avoided because it targets CD19, and the potential implications for CAR-T cell therapy if the patient loses CD19, or its expression density decreases, has not been thoroughly studied [71]. For these patients, GemOx +/− R may be a suitable option. The three regimens (pola-RB, tafa-len and R-GemOx) are more efficacious in relapsed than in primary refractory patients. Its inclusion in clinical trials is especially recommended for the latter group of patients. ⁴ The selection of treatment must be individualized according to patient’s characteristics and the toxicity profile of each agent or regimen. ⁵ Liso-cel is approved by the FDA, but not by the EMA, for this indication.