An example is the Smart Start trial recently presented at the 2019 American Society of Clinical Oncology (ASCO) annual meeting and the 15th International Conference on Malignant Lymphoma 2019 (15-ICML) meeting. The data suggest that the use of rituximab, lenalidomide, and ibrutinib (RLI) as an induction treatment (prior to any chemotherapy) of non-germinal center (non-GCB) DLBCL results in high overall response rates (ORR) of 86% (after two rounds of RLI) and 100% when followed by chemotherapy treatment. Links to the summary of the Smart Start trial data (click here) and to the interview with Dr. Westin (click here) are provided.
Prof. Jäger highlighted that maintenance therapy is currently the only area where chemotherapy-free treatment options have demonstrated a benefit, referring to the REMARC trial. In REMARC, elderly patients with DLBCL showed significant improvement in progression-free survival (PFS) when lenalidomide maintenance was given for 24 months following a complete or partial response to R-CHOP. In terms of chemotherapy-free treatment for relapsed/refractory (R/R) DLBCL, several options have been used, including ibrutinib, ibrutinib+nivolumab, lenalidomide, lenalidomide+obinutuzumab, EZH2 inhibitor, blinatumomab, pembrolizumab, obinutuzumab+venetoclax, tafasitamab+lenalidomide, and CAR-T cells. A summary table of ‘true chemo-free’ therapies for R/R DLBCL as shown by Prof. Jäger can be accessed here (Link to Jager slides from LHSS)
Prof. Jäger pointed out the variability of responses to these R/R chemotherapy-free therapies and the need to consider patient genetic profiles to determine appropriate options. He concluded by presenting two case studies of patients who were treated with truly personalized chemotherapy-free drugs, chosen to match their tumor mutation. A patient with MYD88 mutated DLBCL achieved a lasting response to ibrutinib therapy, and another with MUM1 positive DLBCL remains in third CR after treatment with lenalidomide. Prof. Jäger suggested that functional drug screening may be the way forward for the chemotherapy-free treatment of patients with DLBCL.