The use of bispecific antibodies (BsAbs) in the treatment of relapsed/refractory multiple myeloma (MM) is showing early promising overall response rates in heavily pre-treated patients. Infectious complications related to the use of BsAbs are not well described. We conducted a pooled analysis that included all single agent BsAbs used in MM with no prior use of different BsAbs. A total of 1185 MM patients (number of trials, n=11) were treated with a BsAb in the studied period (71.6% of patients treated with an agent targeting B-cell maturation antigen (BCMA). Pooled median follow up was short at 6.1 months (7.5 vs. 5.2 months for BCMA vs. non-BCMA BsAbs, respectively). Adverse events (AEs) of interest included all grade neutropenia in 38.6% (n=441/1143), all grade infections in 50% (n=542/1083), all grade cytokine release syndrome (CRS) in 59.6% (n=706/1185), grade III/IV neutropenia in 34.8% (n=372/1068), grade III/IV infections in 24.5% (n=272/1110), grade III/IV pneumonia in 10% (n=52.4/506), and grade III/IV coronavirus 2019 (COVID-19) in 11.4% (n45.4/395). Non-BCMA targeted bispecific antibodies were associated with lower grade III/IV neutropenia (25.3% vs. 39.2%, P=0.001) and lower grade III/IV infections (11.9% vs. 30%, P=0.01) when compared to BCMA-targeted bispecific antibodies. Hypogammaglobulinemia was reported in 4 studies with prevalence of 75.3% (n=256/340) with intravenous immunoglobulin used in 48% (n=123/256). Death was reported in 110 patients of which 28 (25.5%) were reported to be secondary to infections. Certain precautions should be used when using BsAbs to mitigate the risk and/or identify and treat infections promptly.

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A 41-year-old woman with no significant past medical history presented to the hospital with complaints of nausea, vomiting, and generalized weakness over two weeks. The patient did not seek medical attention as she assumed that her symptoms willwould resolve. Following her initial denial of drug abuse and her abnormal urine drug screening, we discussed the findings with the patient. She later admitted to using both amphetamines and marijuana. This led us to take a detailed social history that revealed an unexpected event.

Venous thromboembolism (VTE) is a common condition whose pathophysiology is explained by Virchow's triad with stasis, hypercoagulability, and endothelial injury. Direct oral anticoagulants (DOACs) showed non-inferiority when compared with conventional treatment using subcutaneous low molecular weight heparin (LMWH) and warfarin, but treatment failure is a concern and remains a challenge for physicians. In our case report, we present a patient who had VTE in the form of a saddle pulmonary embolus while on apixaban.

Background: Classic therapeutic (RX) oncology principles demand radiographic response or durable stable disease as surrogates of overall survival (OS) prolongation, the ultimate metric of Rx benefit. Progressive disease (PD), however, is an undisputed indication of treatment failure. Immune Oncology (IO) trials reporting individual patient outcomes using swimmers' plot (SP) suggest substantial OS subsequent to PD, unprecedented pre-IO. Hypothesis: Unrecognized phenomenon of OS benefit in the setting of radiographic PD, is tissue-agnostic and prevalent (>15%). Methods: We conducted a retrospective review of IO monotherapy trials in 3 cancers if SP were reported. Percentage of PD patients (Pts) surviving beyond defined time landmarks is reported (Table). Results: Realizing that 3rd or subsequent Rx lines rarely provide > 6 months OS duration in most cancers, our results indicate that 2/3rd of IO-treated pts, regardless of histology, or line of therapy are performing significantly better than expected; 1/3rd surviving > 1 year beyond PD. Discussion: In IO, radiographic bulk may increase despite undeniable OS benefit (in years). We likely underestimated this phenomenon since pts with PD at 1st assessment aren't included in the SP, and with longer follow up, OS of PD pts is likely to improve with longer time to manifest it. This phenomenon–we term 'Disguised Responders' (DRs)–challenges an oncology principal. DRs needs to be considered by clinicians and future drug developers to accurately identify putative novel drugs. A plausible mechanism of DRs posits that 'virulence' of a given subclone, regardless of size or bulk, dictates Rx outcome. Virulence may operate through cachexia-induction, propensity to metastasize or metabolic adaptability, to name a few. Novel experimental approaches are desperately awaited to probe and measure virulence of different tumor subclones in future drug evaluations. Table 1. Clinical Trials of IO Monotherapy Number and (%) of pts surviving beyond clinical PD (months) Tumor Rx Line 1st Author/Yr N PD (n) <6 6-11 12-23 24-35 36-47 > 48 NSCLC* 2nd + Topalian ''19 22 12 1 2 4 1 4 1st + Fredinandus ''21 45 2 1 1 1st + Kim ''22 139 22 13 5 3 N/A Bilger ''22 18 10 3 4 3 2nd Dart ''21 7 3 2 1 2nd + Tozuka (MR) ''20 11 11 4 6 1 2nd + Tozuka (PD) ''20 51 51 29 12 7 2 1 2nd + Waterhouse ''20 39 38 16 14 4 4 Subtotal 332 149 63 (42%) 44 (30%) 28 (18%) 4 (3%) 5 (3%) 4 (3%) Melanoma 1st + Warburton ''20 70 13 1 4 3 4 1 2nd + Topalian ''19 34 21 1 2 10 4 4 2nd + Weber ''15 38 4 2 1 1 2nd + Dimitriou ''21 125 9 3 4 2 Subtotal 267 47 3 (6%) 8 (17%) 10 (21%) 17 (36%) 5 (11%) 4 (8.5%) RCC** 2nd + Topalian 19'' 10 7 1 1 2 3 7 15% 15% 30% 42% Total 609 203 33% 25% 15% 10% 6% 5.4% *Non-small cell lung cancer. ** Renal Cell Carcinoma Citation Format: Farah Mazahreh, Liyan Mazahreh, Brad Fugere, Ahmad Mazin Safar. Unprecedented tumor: immune interaction–clinical and drug-development implications. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 4385.