TEST:

MSK-IMPACT Heme

Introduction : High grade B-cell lymphomas with MYC, BCL2 and/or BCL6 rearrangements (R) are a group of aggressive lymphomas with poor prognosis when treated with R-CHOP and generally present at advanced stage with a high risk of CNS relapse...Indeed, there was no clear impact of CNS prophylaxis/IT-chemotherapy as relapses were distributed equally between those who did or did not receive prophylaxis. Larger multicenter studies dedicated to this unique population is warranted and our study supports the ongoing separation of MYC/BCL6-R for further research purposes.

Conclusion : The rare NPM1 mutation subtypes share a similar pattern of co-mutations with the common NPM1 type A, are similarly affected by the FLT3 status and by the presence of a TM-phenotype and feature similar OS. Publicly available datasets can be exploited to collect information on rare entities which would be otherwise poorly characterized.

Several patients with prior melphalan exposure have SBS99 evident in several biopsies, consistent with single cell expansion from MM cells surviving transplant and subsequently seeding in multiple sites...EMD are more complex in general than PMD, while IMD shows only trends to increased genomic aberration compared with BM. Ongoing analyses include an expansion in WGS samples, and correlation of genomic features with clinical response to therapy.

BsAb and CAR-T may overcome individual standard genomic RF, however harboring multiple genomic RF remains adverse. Clinically available extended genomic characterization predicts response better than FISH alone in this large cohort treated with BsAb/CAR-T. This work will extend into pre-/post-therapy whole genome sequencing for more granular data analysis.

Several melphalan-exposed patients had SBS99 evident in the phylogenetic tree trunk of multiple biopsies, consistent with single cells surviving transplant and subsequently seeding in multiple sites. PMD and EMD demonstrate multiple features of genomic complexity when compared with BM-based myeloma, including emerging copy number aberration, mutational burden, and complex structural variants. Ongoing studies include expanding the WGS dataset, and correlation of genomic features with clinical response to therapy.

This analysis of IMS using targeted sequencing data, highlighted some possibleassociations between intratumoral microorganisms and lymphoma-specific subtypes, especially in indolentsubtypes of ALCL (BIA- and pc-) compared to systemic ALCL. Further analyses with more cases andconfirmatory techniques might confirm these initial findings. Figure.

"In this cohort, an association with recent history of graft-vs-host disease was identified. These findings should be considered as a potential limitation for the use of nail as normal control but could also provide important diagnostic information regarding the disease process."

"One limitation of the recently presented IRMMa model was an absence of patients prescribed daratumumab-based quadruplet induction, (dara-quads; daratumumab, lenalidomide, dexamethasone with carfilzomib [DKRd] or bortezomib [DVRd]). Among 234 patients analyzed, 86 patients received DKRd and 148 DVRd. Overall median follow-up was 1.4 years (y); 4.2y with DKRd (IQR 1.9-4.7, max 5.7) and 1y with DVRd (IQR 0.5-1.4, max 3.4). 25 patients progressed following DKRd and 20 following DVRd, with 9 progressing during induction chemotherapy."

Prior to MN diagnosis, ten patients (67%) received etoposide and seven patients (47%) received autologous stem cell transplant (ASCT) (six with BEAM, one with cyclophosphamide plus total body irradiation). Herein we report the CI of MN in a cohort of patients with TCL, with particular attention to nodal TFH cell lymphomas given known CH mutations and the genotoxic stress of combination chemotherapy. As more patients have prolonged survival after initial therapy for TCL, further analysis, including baseline genetics and prospective characterization for clonal expansion and acquired mutations during therapy, could identify those at highest risk for developing a MN. Further characterization of our cohort and comparison to patients who did not develop a MN is ongoing.

Initial treatment included monoclonal antibody + chemotherapy (57%), single-agent rituximab (17%), chemotherapy (2%), radiotherapy alone (8%), and other treatments (5%)... A cohort of 292 pts was analyzed. Genomic alterations were identified in the 7 genes. Median age of diagnosis was 57 years (range 26-92) with a slight male predominance (53%).