Background Relapsed and refractory multiple myeloma (RRMM) remains a major challenge. With each relapse, patients (pts) experience decreased response duration leading to shortened survival. Pts with triple-class refractory disease (refractory to one class of the following: immunomodulatory agents (IMiDs), proteasome inhibitors (PI) and anti-CD38 monoclonal antibody) have a poor prognosis. Belantamab mafodotin is a first-in class B-cell maturation antigen (BCMA) antibody-drug conjugate. The aim of this study was to analyze the clinical outcomes of belantamab/dexamethasone (Bd) in triple-class RRMM. Patients & Methods Twenty-eight pts with triple-class RRMM receiving Bd were identified at University of Kansas Health System between October 2019 and June 2021 and reviewed retrospectively. These pts received belantamab 2.5 mg/kg IV every 3 weeks and dexamethasone (20-40) mg PO weekly. Descriptive analyses were performed on available data for patient characteristics. Survival curves were generated using the Kaplan-Maier method. Responses were evaluated using the International Myeloma Working Group (IMWG) criteria. Results The median age was 67 yrs (42-85). Eleven pts (39%) had IgG isotype, 14 pts (50%) had R-ISS stage III disease, 20 pts (71%) had high-risk cytogenetics, and 13 pts (46%) had extramedullary disease (EMD). Patients characteristics are summarized in Table 1. Median number of Bd cycles received was 3 (2-18). The median number of previous lines of therapy was 5 (3-15). All pts were triple-class refractory, whereas 15 pts (54%) were penta-refractory. Twenty-one pts (75%) received autologous stem cell transplant, and 8 pts (29%) had previously received BCMA-targeted therapy. The response rate for all pts was 46% with 18% achieving very good partial response and better. Median follow-up was 7.4 months. Median progression-free survival (PFS) was 4.9 months, while median overall survival (OS) was 7.4 months. The response rates are summarized in Table 2. Keratopathy was one of the most common adverse events (AEs), occurring in 23 (82%) pts, 13 (56%) pts had grade 3 or 4 keratopathy. Nineteen patients (68%) required dose reduction or delay due to keratopathy. Other common AEs included: anemia (83%), thrombocytopenia (70%), neutropenia (30%), and elevated liver function tests (53%). Eighteen patients (64%) discontinued due to progression of disease or death. No treatment-related mortality was noted in this review. Conclusion Our analysis demonstrates a reasonable efficacy of Bd in those who are heavily treated triple-class RRMM patients in the real world. Keratopathy remains a challenging AE and the main cause of dose reduction and delay. Figure 1 Figure 1. Disclosures Atrash: AMGEN: Research Funding; Jansen: Research Funding, Speakers Bureau; GSK: Research Funding. Mahmoudjafari: GSK: Membership on an entity's Board of Directors or advisory committees; Omeros: Membership on an entity's Board of Directors or advisory committees; Incyte: Membership on an entity's Board of Directors or advisory committees. McGuirk: Magenta Therapeutics: Consultancy, Honoraria, Research Funding; Allovir: Consultancy, Honoraria, Research Funding; Kite/ Gilead: Consultancy, Honoraria, Other: travel accommodations, expense, Kite a Gilead company, Research Funding, Speakers Bureau; Gamida Cell: Research Funding; Novartis: Research Funding; EcoR1 Capital: Consultancy; Juno Therapeutics: Consultancy, Honoraria, Research Funding; Novartis: Research Funding; Fresenius Biotech: Research Funding; Astelllas Pharma: Research Funding; Bellicum Pharmaceuticals: Research Funding; Pluristem Therapeutics: Research Funding.

LCNEC of the lung comprises a small proportion of pulmonary malignancies. Traditionally, they have been classified based on histologic and immunohistochemistry characteristics with features of small cell and non-small cell lung cancer. The treatment outcome of advanced-stage LCNEC of the lung is poor with response rates ranging from 34 to 46% with platinum doublets, median progression-free survival (mPFS) ranging between 4.4 and 5.8 m, and median overall survival (mOS) ranging from 8 to 12.6 m. The optimal treatment strategy for LCNEC is debated given limited data and different outcomes based on chemotherapy type reported in the available literature. Recently, genomic profiling with Next Generation Sequencing (NGS) has been able to sub-classify LCNEC as SCLC-like or NSCLC-like. Treatment based on this sub-classification has improved outcomes by using SCLC and NSCLC regimens based on their genomic profile in retrospective analysis. Future studies in LCNEC of the lung should incorporate this new molecular sub-classification as stratification and possibly include SCLC-like LCNEC into SCLC studies and NSCLC-like into NSCLC studies.

Many patients with plasma cell disorder (PCD) on active treatment with severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) require hospitalization, with an increased mortality rate over healthy adults. The FDA approved two mRNA vaccines against SARS‐CoV‐2: BNT162b2 and mRNA‐1273. To assess the efficacy of vaccination in patients with PCD, retrospectively, we identified all patients on active treatment. A total of 149 patients were included. Neutralizing antibodies (NAbs) levels against SARS‐CoV‐2 adequate, intermediate, and no response were observed in 42%, 32%, and 26%, respectively. Low NAbs were seen in patients on daratumumab combinations or anti‐BCMA therapy, low lymphocytes, and low IgG levels. Twenty‐three (15%) patients have SARS CoV‐2, while 8% required hospitalization, majority of these patients had intermediate or no response based on NAbs levels. Therefore, checking NAbs may be clinically helpful in identifying patients' responses. Further prospective studies should ascertain the value of a third vaccine dose in this population.

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Systemic mastocytosis (SM) is a heterogeneous group of diseases characterized by the proliferation of abnormal mast cells in the bone marrow or other organs. 1 Activating mutations in KIT are found in the majority of patients, with the KIT D816V mutation being the most common .2 While patients with indolent systemic mastocytosis (ISM) have a life-expectancy similar to the general population, approximately 40-53% of patients with SM have an associated hematologic neoplasm (SM-AHN) with a median overall survival of 2 years. 1-3 Treatment of SM-AHN is primarily directed at the AHN as this determines overall survival, with symptomatic treatment for SM if needed.4 Midostaurin is the only approved agent for SM with KIT K816V mutation and overall response rates in SM-AHN are <60%. 5-6 No agents are approved beyond first line. We present the unique case of an 81-year-old male who presented with SM and low risk CMML (46 XY with ASXL1, KIT (p.D816V), SRSF2, TET2, RUNX1, MSH2, CBL). He received first line therapy with midostaurin 100 mg twice a day and achieved an early partial response but progressed after 7 months with increasing mastocytosis burden, rising tryptase and transformation of CMML to AML (image 1). He was subsequently treated with combination standard dose decitabine and venetoclax. The best response for the AML was CRi which was achieved after the first cycle and continues to be ongoing over 12 months since initiation of therapy. We also observed objective response of the SM disease burden on BM exams and steady decline in tryptase levels that continues to be ongoing (figure 1 and 2). Best response by IWG-MRT-ECNM is partial remission achieved after 9 months of therapy. SM-AML is rare and can be diagnosed concomitantly with SM or as a transformation of an SM-AHN. Additional mutations are often present, with the presence of ASXL1 and RUNX1 being associated with a particularly poor prognosis.7-8 Treatment for SM-AML is similar to standard AML treatment with allogenic stem cell transplantation (ASCT) being preferred in those able to tolerate it. While ASCT is the only potential cure for both diseases, SM often persists even with response of the AML.9-11 In a case report of 11 patients with SM-AML, 8 patients received induction chemotherapy with cytarabine and daunorubicin while 3 received induction with cytarabine and idarubicine. Seven patients received ASCT but five relapsed and eventually expired. None of the 3 long-term survivors had a c-KIT D816V mutation and two of them received ASCT. In 7 out of the 10 patients in CR or after ASCT, SM persisted. 9 In 2 case reports of SM-AML with D816V mutation, treatment consisted of induction and consolidation chemotherapy plus dasatinib and chemotherapy with ASCT and dasatinib. Both patients achieved HCR but again had persistent SM.10-11 The activity of hypomethylating agents (HMA) with venetoclax has not previously been reported in patients with SM-AML. Venetoclax plus either HMAs or low-dose cytarabine was approved for the treatment of AML in the elderly and those unable to tolerate induction chemotherapy in 2018. Venetoclax is an oral inhibitor of BCL-2, an antiapoptotic protein important in the pathophysiology of AML. In the initial study, the CR/Cri rate was 68% with a median time to response of 1.2 cycles. Venetoclax has also shown activity in other hematologic malignancies, including chronic lymphocytic leukemia, and non-Hodgkin's lymphoma.12 SM-AML is an aggressive disease with limited treatment options. To our knowledge, this is the first report of sustained response of both SM-AHN and AML using a HMA and venetoclax. Given the difference in response time and dynamics, this treatment combination seems to have activity in both disease clones independently. This case suggests a potential treatment option for this unmet need and demonstrates the importance of research into the utility of venetoclax in mast cell neoplasms. Disclosures Yacoub: Ardelyx: Current equity holder in publicly-traded company; Dynavax: Current equity holder in publicly-traded company; Cara Therapeutics: Current equity holder in publicly-traded company; Hylapharm: Current equity holder in private company; Incyte: Speakers Bureau; Agios: Honoraria, Speakers Bureau; Novartis: Speakers Bureau; Roche: Other: Support of parent study and funding of editorial support.