Division of Hematology, The University of Colorado Anschutz Medical Campus Aurora, CO.
Am Soc Clin Oncol Educ Book. 2023 Jan;43:e390802. doi: 10.1200/EDBK_390802.
Most patients with diffuse large B-cell lymphoma (DLBCL) will be cured with up-front chemoimmunotherapy, but 30%-40% of patients will experience relapsed disease. Historically, salvage chemotherapy followed by autologous stem-cell transplant (ASCT) was the mainstay of treatment for these patients. However, research has demonstrated that patients with primary refractory or early relapsed (R/R; high-risk) DLBCL do not benefit from ASCT, prompting investigation into other options. With the advent of chimeric antigen receptor (CAR) T-cell therapy, treatment of R/R DLBCL has changed dramatically. With positive outcomes in the TRANSFORM and ZUMA-7 trials with manageable toxicity profiles, approval was obtained for lisocabtagene maraleucel (liso-cel) and axicabtagene ciloleucel (axi-cel) as second-line therapies for high-risk R/R DLBCL. However, these trials required patients to be medically fit for ASCT. In PILOT, liso-cel was deemed a reasonable treatment option for R/R transplant-ineligible patients. We recommend either axi-cel or liso-cel for fit patients with high-risk R/R DLBCL or liso-cel for unfit R/R patients as a second-line therapy. If CAR T-cell therapy is not an option, we recommend consideration of either ASCT if the patient has chemosensitive disease and is fit or clinical trial if the patient is unfit or has chemoresistant disease. If trials are not an option, alternative treatments are available. With the advent of additional therapies such as bispecific T-cell-engaging antibodies, the treatment landscape of R/R DLBCL may be upended. There continue to be many unanswered questions in the management of patients with R/R DLBCL, but given the promise of cellular therapies, outcomes are more optimistic in this group with historically dismal survival.
大多数弥漫性大 B 细胞淋巴瘤（DLBCL）患者经 upfront 化疗免疫治疗可被治愈，但仍有 30%-40%的患者会出现疾病复发。既往，挽救化疗后自体造血干细胞移植（ASCT）是这些患者的主要治疗方法。然而，研究表明，原发性难治或早期复发（R/R；高危）DLBCL 患者不能从 ASCT 中获益，促使人们探索其他选择。随着嵌合抗原受体（CAR）T 细胞治疗的出现，R/R DLBCL 的治疗发生了巨大变化。在 TRANSFORM 和 ZUMA-7 试验中取得了阳性结果，且毒性谱可管理，批准了 liso-cel 和 axi-cel 用于高危 R/R DLBCL 的二线治疗。然而，这些试验要求患者适合进行 ASCT。在 PILOT 试验中，liso-cel 被认为是不适合进行 ASCT 的 R/R 患者的合理治疗选择。我们建议适合的高危 R/R DLBCL 患者选择 axi-cel 或 liso-cel，不适合的 R/R 患者选择二线治疗 liso-cel。如果不能进行 CAR T 细胞治疗，我们建议如果患者有化疗敏感疾病且身体状况良好，则选择 ASCT，如果患者身体状况不佳或患有耐药性疾病，则选择临床试验。如果没有临床试验，还有其他替代治疗方案。随着双特异性 T 细胞结合抗体等其他治疗方法的出现，R/R DLBCL 的治疗格局可能会被颠覆。R/R DLBCL 患者的管理仍存在许多未解决的问题，但鉴于细胞疗法的前景，在这个历史上生存率极差的患者群体中，结果更加乐观。
