Jatin J Shah1, Rafat Abonour2, Christina Gasparetto3, James W Hardin4, Kathleen Toomey5, Mohit Narang6, Shankar Srinivasan7, Amani Kitali7, Faiza Zafar7, E Dawn Flick7, Robert M Rifkin8. 1. Department of Lymphoma/Myeloma, M.D. Anderson Cancer Center, Houston, TX. 2. Department of Hematology/Oncoloy, Indiana University Simon Cancer Center, Indianapolis, IN. 3. Department of Hematologic Malignancies and Cellular Therapy, Duke University Medical Center, Durham, NC. 4. Department of Epidemiology and Biostatistics, University of South Carolina, Columbia, SC. 5. Department of Hematology and Medical Oncology, Steeplechase Cancer Center, Somerville, NJ. 6. Department of Hematology and Medical Oncology, US Oncology Research, Maryland Hematology Oncology, Columbia, MD. 7. US Medical Affairs, Celgene Corporation, Summit, NJ. 8. US Oncology Research, The Woodlands, TX; Medical Oncology/Hematology, Rocky Mountain Cancer Centers, Denver, CO. Electronic address: Robert.Rifkin@usoncology.com.
Abstract
BACKGROUND: The performance of multiple myeloma (MM) therapies in a general patient population and specific eligibility criteria that might limit enrollment into randomized controlled trials (RCTs) have not been evaluated in depth. This study aimed to determine if improvements seen with MM therapies in RCTs are reflected in the general patient population and to identify eligibility criteria that can be modified to increase enrollment. PATIENTS AND METHODS: The Connect MM Registry is a prospective observational cohort study of patients with newly diagnosed MM (NDMM) in the United States. Using common RCT exclusion criteria collected from 16 published studies, patients in the registry were categorized according to their eligibility for inclusion in RCTs. RESULTS: On the basis of common criteria, 563 of 1406 of registry patients (40.0%) are ineligible for RCTs. Criteria leading to exclusion included M-protein ≤ 1.0 g/dL (25.2%), creatinine > 2.5 mg/dL (13.9%), low absolute neutrophil count (10.0%), and low hemoglobin (9.6%). Significantly more RCT-ineligible versus RCT-eligible patients had hypercalcemia (11.0% vs. 5.5%), elevated creatinine levels (38.9% vs. 6.2%), low hemoglobin levels (59.5% vs. 39.5%), or International Staging System stage III disease (40.1% vs. 22.1%; P < .001 for all comparisons). RCT-ineligible patients had a lower 3-year survival rate than RCT-eligible patients (63% vs. 70%). The incidence of serious adverse events was similar between groups. CONCLUSION: Of patients with NDMM enrolled in the Connect MM Registry, 40% are ineligible for RCTs. This study provides insight into potential modifications of standard eligibility criteria that can lead to improved RCT design and accelerated enrollment.
BACKGROUND: The performance of multiple myeloma (MM) therapies in a general patient population and specific eligibility criteria that might limit enrollment into randomized controlled trials (RCTs) have not been evaluated in depth. This study aimed to determine if improvements seen with MM therapies in RCTs are reflected in the general patient population and to identify eligibility criteria that can be modified to increase enrollment. PATIENTS AND METHODS: The Connect MM Registry is a prospective observational cohort study of patients with newly diagnosed MM (NDMM) in the United States. Using common RCT exclusion criteria collected from 16 published studies, patients in the registry were categorized according to their eligibility for inclusion in RCTs. RESULTS: On the basis of common criteria, 563 of 1406 of registry patients (40.0%) are ineligible for RCTs. Criteria leading to exclusion included M-protein ≤ 1.0 g/dL (25.2%), creatinine > 2.5 mg/dL (13.9%), low absolute neutrophil count (10.0%), and low hemoglobin (9.6%). Significantly more RCT-ineligible versus RCT-eligible patients had hypercalcemia (11.0% vs. 5.5%), elevated creatinine levels (38.9% vs. 6.2%), low hemoglobin levels (59.5% vs. 39.5%), or International Staging System stage III disease (40.1% vs. 22.1%; P < .001 for all comparisons). RCT-ineligible patients had a lower 3-year survival rate than RCT-eligible patients (63% vs. 70%). The incidence of serious adverse events was similar between groups. CONCLUSION: Of patients with NDMM enrolled in the Connect MM Registry, 40% are ineligible for RCTs. This study provides insight into potential modifications of standard eligibility criteria that can lead to improved RCT design and accelerated enrollment.
Authors: Evangelos Terpos; Karthik Ramasamy; Nadjoua Maouche; Jiri Minarik; Ioannis Ntanasis-Stathopoulos; Eirini Katodritou; Matthew W Jenner; Hana Plonkova; Maria Gavriatopoulou; Grant D Vallance; Tomas Pika; Maria Kotsopoulou; Jaimal Kothari; Tomas Jelinek; Efstathios Kastritis; Robin Aitchison; Meletios A Dimopoulos; Athanasios Zomas; Roman Hajek Journal: Ann Hematol Date: 2020-04-01 Impact factor: 3.673
Authors: Yan-Ting Chen; Erik T Valent; Erik H van Beers; Rowan Kuiper; Stefania Oliva; Torsten Haferlach; Wee-Joo Chng; Martin H van Vliet; Pieter Sonneveld; Alessandra Larocca Journal: Int J Lab Hematol Date: 2021-08-26 Impact factor: 3.450
Authors: H Tilman Steinmetz; Moushmi Singh; Andrea Lebioda; Sebastian Gonzalez-McQuire; Achim Rieth; Martina Schoehl; Wolfram Poenisch Journal: Oncol Res Treat Date: 2020-07-21 Impact factor: 2.825
Authors: Shakira J Grant; Hira S Mian; Smith Giri; Melina Boutin; Lorenzo Dottorini; Nina R Neuendorff; Jessica L Krok-Schoen; Nikita Nikita; Ashley E Rosko; Tanya M Wildes; Sonja Zweegman Journal: J Geriatr Oncol Date: 2020-12-17 Impact factor: 3.599