tbuckley/cabot-search huggingface dataset:
Real-world outcomes (RWO) with tandem transplantation in patients (pts) with newly diagnosed multiple myeloma (NDMM).
Authors: Harsh Parmar, Anna Barcellos, Noa Biran, Pooja Phull, David H. Vesole, Andrew J. Belli, Laura L. Fernandes, Eric Hansen, Christina Zettler, Ching-Kun Wang, Stefanie Goran, Courtney Anderson, Kimberley Doucette, Thomas S Gunning, Andrew Ip, David Samuel DiCapua Siegel
Journal: Journal of Clinical Oncology (2024)

7564 Background: Stem cell transplant (SCT) followed by maintenance therapy (MT) is the standard of care for transplant eligible NDMM pts. Tandem transplantation has been found to have progression free (PFS) and overall survival (OS) benefit particularly for patients with high-risk cytogenetic abnormalities (HRCA). However, this modality remains under-utilized in clinical practice. We report RWO with tandem transplant (TT) in comparison with single SCT followed by MT (STM). Methods: We performed a multi-center, retrospective, observational study using the de-identified COTA real-world database derived from the EMRs of US centers. Pts with NDMM from 1/1/2012 to 1/1/23 were included in the study. Kaplan-Meier method was used to evaluate time to next treatment (TTNT), OS, follow-up time (reverse OS endpoint), and report log-rank test p-values. TTNT was defined in two ways: time from 1st SCT (2nd if TT) to the earliest of initiation of next line of therapy (LOT) or death (TTNT1) and the time from 2nd LOT post-SCT to the earliest of initiation of next LOT or death (TTNT2). A propensity score (PS) model was used to compare study cohorts, and hazard ratios (HRs) were estimated using the Cox proportional hazards method. HRCA were defined as pts with 17p(-), t(4;14), t(14;16), t(14;20) and 1q+. Results: 1117 pts met the study criteria. Median age at diagnosis was 60 yrs. 56.9% were male, 68.9% were White, and 32% had HRCA. 937 pts received STM and 180 pts received TT with median follow-up time of 68 months (mos) (95% CI: 65.4, 71.9) and 39 mos (95% CI: 31.9, 50.1), respectively. Median TTNT1 for TT vs STM was 52.7 vs 51 mos, (p=0.85), respectively. Median TTNT2 for TT vs STM was 33.9 vs 11.8 mos, (p&lt;0.001). respectively. Median OS for TT vs STM was not reached (NR) vs 108.1 mos, (p&lt;0.001), respectively. In the PS model, the TT group had significantly lower hazard of TTNT2 and OS events (HRs 0.49 and 0.47, p&lt;0.001 and p=0.01, respectively) as compared to STM. Conclusions: Our study demonstrates significant improvement in unadjusted TTNT2 and OS RWO for TT pts, despite higher incidence of HRCA compared to STM pts. PS analysis demonstrated a similar effect with decreased HRs for TT. OS is an extremely difficult primary outcome to achieve in MM RCTs where survival may have to be collected for decades. Thus, our large study of RWO with long-term follow-up is valuable. [Table: see text]
Rituximab, chidamide, and zanubrutinib (ZCR) ± CHOP as a regimen for treatment naive (TN) double-expressor DLBCL (DE-DLBCL).
Authors: Zhiming Li, Peng Sun, Yirong Jiang, Xiangjun Fu, Lu Zhang, Hang Yang
Journal: Journal of Clinical Oncology (2024)

e19053 Background: DLBCL patients with co-expression of MYC (≥40%) and BCL2 (≥50%) by immunohistochemistry are considered as DE-DLBCL. The prognosis of DE-DLBCL is usually worse than DLBCL-NOS. The Smart Start trial had established the feasibility of chemotherapy-free targeted therapy before 1L chemotherapy. The BTK inhibitor Zanubrutinib (Z) or epigenetic drug Chidamide (C) with R-CHOP regimen has a potential synergistic effect in the treatment of DE-DLBCL. Under the inspiration of Smart Start, this trial aim to explore the feasibility of ZCR±CHOP regimen in TN DE-DLBCL. Methods: This is a multicenter, open-label, single-arm phase 2 study (NCT05527912) conducted in China. If patients achieve complete response (CR) after cycle-2 (C2), ZCR will be continued for up to 8 cycles. Otherwise, ZCR-CHOP will be given for another 6 cycles. The primary endpoint is CR rate at the end of treatment (CRR-EOT); secondary endpoints included ORR (overall response rate) ,2y-PFS, and 2y-OS. Plasma samples were collected at baseline, C2 and the EOT. In evaluable samples, circulating tumor DNA (ctDNA) assays were performed. Results: From February 2023 till now, 34 TN DE-DLBCL patients were enrolled, with 32 patients evaluable. The median age was 52y (range: 22-68), 55.9% were male, 79.4% were Non-GCB (Table 1). 12 patients who achieved CR by C2 were continued with RCZ chemo-free therapy, and CHOP were added to the 14 PR and 3 SD patients. In the 32 evaluable patients, ORR after C2 of RCZ was 81.25% (26/32, CR 37.5%, PR 43.75%, SD 9.4%, PD 9.4%). Up to now, 12 patients have completed 8 courses (C8) and all of them have achieved CR, both ORR and CR are 100% (12/12). 3 patients withdrew due to PD. For safety information in the trial, 64.3% patients reported grade (G)-3/4 AEs. In the Chemo-Free subgroup, only 4 patients (36.4%, 4/11) reported G-3/4 AEs. the majority of G-3/4 AEs is hematological events, including leukopenia, neutropenia and thrombocytopenia. The CR rate at C2 was 66.7% (6/9) in patients with negative baseline ctDNA results. The patients with BCL6 fusion of ctDNA at baseline were more prone to PD (3/4, 75.0%). Compared to baseline, plasma ctDNA levels decreased significantly after C2. 29 patients were evaluable for ctDNA after C2, 100% (12/12) of C2-CR patients and 58.8% (10/17) of non-C2-CR patients were negative, P=0.023. Compared with Non-C2-CR patients, the number of detected mutations and average VAF level were decreased in C2-CR patients. Conclusions: This trial demonstrates ZCR±CHOP could be a promising regimen with active antitumor effect and acceptable toxicity in TN DE-DLBCL patients. Clinical trial information: NCT05527912 .
Efficacy and safety of GPRC5D-based monotherapies for relapsed/refractory multiple myeloma: A systematic review and meta-analysis.
Authors: Asis Shrestha, Ayush Adhikari, Sandesh Rayamajhi, Sugam Gouli, Jasmine Shrestha, Sujan Niraula, Niraj Neupane, Samer Al Hadidi
Journal: Journal of Clinical Oncology (2024)

e19503 Background: G protein-coupled receptor family C group 5 member D (GPRC5D), a highly expressed receptor in myeloma cells, is one of the novel emerging targets for relapsed/ refractory (R/R) multiple myeloma (MM). Among the GRPC5D therapies, currently one agent talquetamab has been approved while CAR-T therapies are under development. Methods: A literature search using electronic databases Pubmed, Embase, Scopus, Web of Science and Cochrane, including major conference abstracts was conducted from inception to December 31, 2023 focusing on GPRC5D therapies in MM. For multiple reports of the same study, the latest available report of the study describing the efficacy or safety was selected. Only GPRC5D based monotherapies were included, and combination regimens were excluded for this review. Data on safety and efficacy were extracted, evaluated and systematically analyzed using Comprehensive Meta-analysis 3.3. The study protocol was registered with PROSPERO (CRD42024497933). Results: After screening 562 articles, and removing duplicates, total seven studies with 581 patients were included (5 GPRC5D-CAR T studies with 137 patients and 2 GPRC5D-BsAb studies with 444 patients). The pooled overall response rate (ORR) for GRPC5D therapies in this cohort was 77.4%, with best response rate [very good partial response (VGPR) or better] of 59.2%. The pooled incidence rate of cytokine release syndrome (CRS), any grade and Immune effector cell-associated neurotoxicity syndrome (ICANS), any grade, was 78.8% and 9.6% respectively. Grade 3/4 hematological adverse events included neutropenia being the most common (69.6%), followed by thrombocytopenia (36.8%) and anemia (34.2 %). Subgroup analysis was performed for GPRC5D therapies- CAR T and BsAb as shown in the table. Conclusions: GPRC5D based therapies showed high response rates in R/R MM with distinct side effect profile including CRS and cytopenias. Further studies along with follow up of the ongoing trials is needed to understand the long-term outcomes. [Table: see text]
BGB-11417-203: An ongoing, phase 2 study of sonrotoclax (BGB-11417), a next-generation BCL2 inhibitor, in patients with Waldenström macroglobulinemia.
Authors: Hui-Peng Lee, Stephen Opat, John Hrom, David S. Kliman, Paula Marlton, Peng Liu, Chenmu Du, Amber Lussier, Jun Zhang, Haiyi Guo, Steven P. Treon
Journal: Journal of Clinical Oncology (2024)

TPS7090 Background: Bruton tyrosine kinase (BTK) inhibitors and anti-CD20 antibody-based systemic therapy are included within the preferred treatment algorithms for Waldenström macroglobulinemia (WM). However, to date, no treatments have been approved for patients with WM that is refractory to both BTK inhibitors and anti-CD20 therapy. Venetoclax, the first-generation BCL2 inhibitor, has demonstrated clinical activity in patients with relapsed/refractory (R/R) WM (Castillo et al. J Clin Oncol. 2022), but it has no regulatory approvals in WM. Sonrotoclax, a next generation BCL2 inhibitor, is more selective and a more pharmacologically potent inhibitor of BCL2 than venetoclax. In a phase 1 trial, sonrotoclax monotherapy was well tolerated at all dose levels tested up to 640 mg and showed promising evidence of antitumor activity in patients with R/R WM (Soumerai et al. Blood. 2022). Based on the data from these earlier studies, a phase 2 study of sonrotoclax monotherapy in patients with WM has been initiated and is currently recruiting. Methods: BGB-11417-203 (NCT05952037) is an open-label, international, phase 2 study. Eligible patients have histologically confirmed WM that is R/R to both BTK inhibitor therapy and anti-CD20–based systemic therapy combined with chemotherapy or a proteasome inhibitor (PI; Cohort 1); R/R to anti-CD20–based systemic therapy combined with chemotherapy or a PI and who are intolerant to BTK inhibitor therapy (Cohort 2); or R/R to a BTK inhibitor and who are unsuitable for chemoimmunotherapy (Cohort 3). Patients who have received previous treatment with a BCL2 inhibitor are ineligible. Approximately 85 patients will be enrolled across cohorts and will receive sonrotoclax until disease progression, death, unacceptable toxicity, patient withdrawal, loss to follow-up, or study termination. The primary endpoint is major response rate (MRR; defined as partial response or better) in Cohort 1 per IWWM-11 criteria, as assessed by independent review committee (IRC). Key secondary endpoints include MRR assessed by investigator (INV) in Cohort 1 and by IRC and INV in both Cohorts 2 and 3; overall response rate, duration of response, and progression-free survival by IRC and INV; overall survival; and safety and tolerability. Patient recruitment is ongoing in Australia, the US, China, and Europe. Clinical trial information: NCT05952037 .
External validation of the lactate dehydrogenase/albumin ratio as a clinical predictor of overall survival in Peruvians with diffuse large B cell lymphoma.
Authors: Rafael Pichardo-Rodriguez, Brady E Beltran Garate, Denisse Castro-Uriol, Sally Paredes-Noguni, Manuel Vela-Ruiz, Ashley Efrain Alarcon Rozas, Jhony A. De La Cruz-Vargas, Luis Vilela
Journal: Journal of Clinical Oncology (2024)

e19072 Background: The lactate dehydrogenase/albumin ratio (RLA), a potentially promising inflammatory biomarker derived from the division of serum lactate dehydrogenase and albumin values, has shown a strong correlation with overall survival (OS) in patients with diffuse large B-cell lymphoma (DLBCL). However, its validity in our specific population requires confirmation. We aimed to validate the RLA as an early predictor of OS in a cohort of Peruvian patients with DLBCL. Methods: We conducted a retrospective cohort study recruiting consecutive patients diagnosed between 2009 and 2017, with the last follow-up on July 1, 2022, at the National Hospital Edgardo Rebagliati Martins and the Maria Auxiliadora Hospital. The optimal cutoff point for RLA was estimated using ROC curve analysis, and survival curves were plotted and analyzed using Cox regression and Kaplan-Meier methods with the Log-Rank test. Results: A total of 283 patients with a median follow-up of 2.6 (range: 0.02-10.51) years were included. The optimal cutoff point for RLA was established at 23.6. Values below 23.6 were associated with poor OS when comparing survival curves (p&lt;0.001). In the multivariate model, a prognostic association was found between RLA and OS (HR: 3.37, 95% CI: 1.78-6.39, p&lt;0.001). Conclusions: The RLA is confirmed as a valid biomarker in our population for predicting OS in patients with diffuse large B-cell lymphoma (DLBCL), allowing for early evaluation. [Table: see text]
Clinical observation study of recombinant human thrombopoietin in the prevention of chemotherapy-induced thrombocytopenia in patients with aggressive lymphoma.
Authors: Lei Yang, Ting Wang, Zhenling Li, Qi Deng, Wei Yang, Hebing Zhou, Hongmei Jing, Changyong Sun, Liru Wang, Li Bao, Fang Ye, Jie Bai, Lu Si, Jingwen Wang, Hui Liu
Journal: Journal of Clinical Oncology (2024)

e19056 Background: Recombinant human thrombopoietin (rhTPO) has demonstrated efficacy in elevating platelet counts in lymphoma patients suffering from chemotherapy-induced thrombocytopenia. However, the optimal timing for its administration remains to be established. Methods: This prospective, observational, non-randomized, multicenter study aimed to identify the optimal timing for rhTPO intervention in patients with aggressive lymphoma experiencing chemotherapy-induced thrombocytopenia. Participants aged between 18 and 70 years, diagnosed with aggressive lymphoma and chemotherapy-induced thrombocytopenia, were divided into three groups based on their baseline platelet counts. Group 1 received rhTPO when platelet counts fell below 50×10 9 /L but remained above 25×10 9 /L; Group 2 was treated with rhTPO at platelet counts ≥ 50×10 9 /L and &lt; 75×10 9 /L; and Group 3 received rhTPO treatment for platelet counts ≤ 25×10 9 /L. Treatment was discontinued once platelet counts reached ≥ 100×10 9 /L. The primary endpoint was the proportion of patients achieving normalization of platelet counts, the secondary outcomes including platelet nadir values, the incidence of platelet transfusions, and adverse events. Results: Eighty-eight patients were enrolled, with 36 in Group 1, 22 in Group 2, and 30 in Group 3. The groups were comparable in clinical manifestation of age, gender, comorbidities, lymphoma classification, and bone marrow involvement. Normalization of platelet counts was achieved in 69.44%, 81.82%, and 36.67% of patients in Groups 1, 2, and 3, respectively, with Groups 1 and 2 showing significantly higher rates than Group 3 (P&lt;0.05). The mean platelet nadir values were significantly higher in Groups 1 and 2 (28.39±10.19×10 9 /L and 43.23±14.97×10 9 /L, respectively) compared to Group 3 (11.13±6.21×10 9 /L, P&lt;0.01). The incidence of platelet transfusions was notably lower in Groups 1 and 2 (19.44% and 13.64%, respectively) than in Group 3 (70.00%, P&lt;0.01). There were no significant differences in adverse event rates across the groups. Conclusions: Early administration of rhTPO significantly enhances platelet recovery and reduces the need for platelet transfusions in aggressive lymphoma patients with chemotherapy-induced thrombocytopenia.
Survival shifts in multiple myeloma: Evaluating the impact of therapeutic advances and racial disparities after a decade of change.
Authors: Ahmed Hebishy, Joshua Walter Zweigle, Ali Hussain, Mahvish Muzaffar
Journal: Journal of Clinical Oncology (2024)

e19509 Background: Multiple myeloma (MM) is the second most common hematologic malignancy and is considered an incurable disease. However, the last two decades have witnessed the emergence of new therapies that have improved overall survival by several folds. In the current study, we are examining the evolving trends in age-adjusted incidence and relative survival among myeloma patients over the last 20 years, specifically focusing on discerning disparities in these trends based on racial classifications. Methods: We performed a retrospective cohort study using the SEER Plus Data, 12 registries, Nov 2022 Sub (1992-2020) to calculate the age-adjusted incidence and relative survival rate (RSR) of MM in the US in two specific time intervals 2001-2010 &amp; 2011-2020 consistent with changes in MM treatment during 2011-2020 including the emergence of immunomodulatory drugs (IMiDs). The year of diagnosis, sex, and race data were available for each case. We excluded cases diagnosed before 2001 and after 2020. Patients were stratified by sex and categorized into two racial groups: White and Black. The 60-month (5-year) and 116-month (used as a 10-year estimate) RSR and age-adjusted incidence rate were calculated for the cohort and each racial group. We calculated survival utilizing the Kaplan-Meier method. Using the log-rank test, we also found hazard ratios (HR), with the corresponding CI for each racial group stratified by sex. Results: We investigated MM incidence and survival rate trends over two decades while considering gender and race. The age-adjusted incidence rate showed a significant overall increase from 6.5 to 7.4 per 100,000, with changes in gender-specific rates. Higher incidence rates among Black populations were noted. Cohort relative survival analysis revealed improved median survival (53 to 83 months) and increased relative survival rate both at five years (46.4% to 56.3%) and at ten years (28.8% to 40.8%). An investigation based on race revealed substantial improvements among both White and Black populations. The HR (Table) emphasized the improved survival outcomes for patients diagnosed in period two across genders and races. Conclusions: The study highlights the changes in the incidence and survival rates of MM. Notably, MM incidence has seen a significant rise in the last decade, particularly among the Black population. The survival of patients diagnosed between 2011 and 2020 revealed statistically significant improvement at both the 5- and 10-year mark compared to patients diagnosed between 2001 and 2010. [Table: see text]
Association of posterior reversible encephalopathy syndrome with proteasome inhibitors approved for multiple myeloma: Analysis of FAERS database.
Authors: Harkarandeep Singh, Uttamjot Kaur, Niraj Neupane, Himal Kharel, Hassan Saeed, Prabhsimrat Gill, Asis Shrestha
Journal: Journal of Clinical Oncology (2024)

e19515 Background: Proteasome inhibitors (PI) are a class of drugs that are used in the treatment of Multiple Myeloma. There are currently three PIs (Bortezomib, Carfilzomib, and Ixazomib) approved by FDA for this indication. Peripheral neuropathy has been described as one of their most common side effects but the association with another life-threatening neurological disorder, Posterior Reversible Encephalopathy Syndrome (PRES), remains poorly understood. Methods: We conducted a retrospective pharmacovigilance study using the FDA Adverse Event Reporting System database to analyze the risk of PRES associated with various Proteasome Inhibitors. We employed disproportionality signal analysis and calculated the reporting odds ratio with a 95% confidence interval. Results: A total of 79,450 adverse events were found within the FAERS database that were associated with the three FDA approved PIs. PRES accounted for 274 cases, of which 165 cases were in females and 71 cases in males. Majority of patients were adults, with 119 cases between 18-64 years of age, 88 cases above 65 years, and 50 cases with age not specified. Death was reported in 70 cases while 74 cases were marked as having life threatening illness, and 152 cases needed hospitalization. Bortezomib accounted for most cases (202 cases, ROR 6.03, 95% CI 5.3-7.1), followed by Carfilzomib (68 cases, ROR 7.2, 95% CI 5.7-9.1), and Ixazomib (9 cases, ROR 0.99, 95% CI 0.5-1.7). Conclusions: The study helps to shed light on the incidence, and hospital outcomes of PRES associated with various proteasome inhibitors. Significant safety signals were found for Bortezomib, and Carfilzomib. Females were almost 2.5 times more likely to develop PRES compared to males. These findings highlight the importance of keeping a high index of suspicion for PRES while evaluating patients on PIs who present with concerning neurological symptoms.
Incidence of acute kidney injury in patients with relapsed and refractory multiple myeloma treated with teclistamab vs chimeric antigen receptor T-cell therapy.
Authors: Mariam Charkviani, Lisa E Vaughan, Tyler B Sandahl, Yi Lin, Nelson Leung, Sandra M Herrmann
Journal: Journal of Clinical Oncology (2024)

7542 Background: Teclistamab, a novel bispecific monoclonal antibody targeting CD3 and BCMA, exhibits promising effects for patients with relapsed and refractory multiple myeloma (MM). However, rates of acute kidney injury (AKI) associated with this therapy remains inadequately characterized. Methods: This was a retrospective observational cohort study of patients with relapsed refractory MM who received teclistamab or Chimeric Antigen Receptor T-cell Therapy (CAR-T) therapy at Mayo Clinic between 12/1/2022-5/15/2023 and who were not in kidney failure at the time of treatment. The primary endpoint was incidence of AKI during follow-up; secondary endpoints included treatment and recovery from AKI. AKI was defined based on Kidney Disease Improving Global Outcomes criteria as an increase of serum creatinine levels &gt; 1.5 times their baseline value after starting therapy. Cumulative incidences and Cox proportional hazard regression models were used to evaluate time to event data. Results: A total of 64 patients met inclusion criteria for the study (30 received CAR-T and 34 received teclistamab therapy). There were 14 AKI events occurring during follow-up (10 teclistamab [n = 6 stage 1, n = 3 stage 2 and n = 1 stage 3] and 4 CAR-T [n = 3 stage 1 and n = 1 stage 2]). Cumulative incidence estimates of AKI at 120 days after treatment were 32% (95% CI: 14%-47%) for teclistamab patients and 10% (95% CI: 0%-21%) for CAR-T patients. While patients receiving teclistamab were found to be at increased risk of an incident AKI event compared to patients receiving CAR-T therapy, results were not statistically significant (HR (95% CI): 3.38 (0.93-12.31), p = 0.065). Median time to development of AKI was 30 days (IQR 16, 73) in teclistamab and 59 days (IQR 9, 146) in CAR-T patients. Among the 10 patients in the teclistamab group with an AKI event, 4 (40%) had complete renal recovery and 4 (40%) had partial recovery, while among the 4 patients with CAR-T with an AKI event, 2 (50%) experienced complete renal recovery and 2 (50%) experienced partial recovery. Conclusions: Our study showed that almost one third of patients receiving teclistamab therapy for relapsed and refractory multiple myeloma experienced an incident AKI event during follow-up. This finding underscores the importance of monitoring for kidney function in these patients.