623. Mantle Cell, Follicular, and Other Indolent B-Cell Lymphoma—Clinical Studies: Mantle Cell Lymphoma Clinical Trials

Michael Wang, Nirav N. Shah, Alvaro J. Alencar, et al.

Authors Conclusion from the Abstract: LOXO-305 demonstrated promising efficacy in heavily pretreated, poor-prognosis MCL pts following multiple prior lines of therapy, including covalent BTKi. Early efficacy was also observed in BTK-treated WM, as well as heavily pretreated other NHLs. LOXO-305 was well tolerated and exhibited a wide therapeutic index.

Maria Lia Palomba, Leo I. Gordon, Tanya Siddiqi, et al.

Authors Conclusion from the Abstract: In this phase 1 study of patients with R/R MCL, treatment with liso-cel was associated with a low incidence of grade ≥3 CRS and NEs, late onset of CRS/NEs, and promising clinical activity. Dose confirmation is ongoing at DL2 in the MCL cohort.

Zachary D. Epstein-Peterson, Connie Lee Batlevi, Philip Caron, et al.

Authors Conclusion from the Abstract: In a novel approach of sequential immunochemotherapy plus lenalidomide enrolling majority high-risk pts, outcomes for TP53-mutant pts were poor and we did not reach our primary endpoint of 3-yr PFS ≥75%. Among TP53-wt pts, this treatment program was highly effective even among pts with elevated Ki-67 (>=30%) and was associated with a high response rate, a 3-yr rate of PFS of 85%, and a high rate of MRD- at EoT.

A substantial proportion of pts converted to MRD- after receipt of R-HiDAC, highlighting the efficacy of cytarabine in MCL. There was a high rate of MRD- after induction chemoimmunotherapy (Len-R-CHOP + R-HiDAC) at 1E5 (97%) and at 1E6 (80%), and the latter predicted remission duration. Several pts converted from MRD- to MRD+ at 6-mos post-EOT and eventually relapsed, suggesting that a more prolonged period of maintenance may be beneficial. Finally, MRD at 1E6 at 6 mos following EoT predicted response duration.

Mary B. Callanan, Elizabeth Macintyre, Marie-Helene Delfau-Larue, et al.

Authors Conclusion from the Abstract: Pre-ASCT MRD status in both BM and PB is an early predictor of PFS and OS in younger MCL patients receiving ASCT. RM provides longer PFS and OS regardless of MRD status pre- and post-ASCT. Early sequential MRD monitoring at the pre-ASCT treatment phase and directly post-ASCT thus offers strong potential for early clinical outcome prediction, as a surrogate clinical end point, and for MRD-guided, risk-adapted treatment in MCL.

Michael Wang, Jacqueline C. Barrientos, Richard R. Furman, et al.

Authors Conclusion from the Abstract: In heavily pretreated patients, VLS-101 infusions were well tolerated and demonstrated a predictable safety profile consistent with an MMAE-containing ADC. Tumor selectivity was confirmed, with no evidence of ROR1-mediated toxicities or non-MMAE toxicities that would suggest normal tissue binding. Considering all data, the VLS‑101 RDR was 2.5 mg/kg every 3 wk. Efficacy results provide clinical proof of concept for targeting ROR1 with VLS-101 and demonstrate durable objective responses in patients with advanced MCL or DLBCL, including those with prior BTKi or cellular therapies. Phase 1-2 studies of VLS-101 monotherapy and combination therapy in patients with hematological cancers and solid tumors are planned.

Mats Jerkeman, Arne Kolstad, Carsten Utoft Niemann, et al.

Authors Conclusion from the Abstract: At a target dose of venetoclax of 600 mg, and lenalidomide 15 mg, this combination is tolerable and shows efficacy in R/R MCL, although associated with a high degree of neutropenia. Interestingly, a response adapted treatment strategy, by stopping treatment in molecular remission, appears to be feasible, although follow-up is still short.