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Clinical Outcomes and Health-Related Quality of Life (HRQoL) Among Randomized Clinical Trial (RCT)-Eligible and RCT-Ineligible Patients: Results from the Connect® MM Registry

Publication ,  Conference
Wagner, LI; Toomey, K; Ailawadhi, S; Jagannath, S; Gasparetto, C; Durie, BGM; Narang, M; Rifkin, RM; Terebelo, HR; Omel, JL; Hardin, JW ...
Published in: Blood
November 13, 2019

Background: MM clinical trials often have stringent eligibility criteria that limit the enrollment of patients (pts) reflective of the general patient population (Shah, Clin Lymphoma Myeloma Leuk 2017). The Connect® MM Registry, a prospective observational study of pts with newly diagnosed MM (NDMM) in the US, provided the opportunity to examine differences between pts with MM who were identified as RCT-eligible vs -ineligible, to observe the generalizability of clinical trial results to real-world clinical settings. Differences in baseline characteristics, treatment, clinical outcomes, and HRQoL were examined in RCT-eligible and -ineligible pts from this registry, which represents an unselected, broad real-world population.Methods: Pts with NDMM were enrolled at 250 community, academic, and government sites. Eligible pts were ≥18 y of age with symptomatic MM diagnosed ≤2 months preenrollment per the International Myeloma Working Group (IMWG) criteria. For this analysis, pts were considered ineligible for RCT per the following key exclusion criteria previously described: absolute neutrophil count ≤1.5 × 109/L, platelet count ≤75 × 109/L, creatinine >2.5 mg/dL, AST/ALT >3 times the ULN, peripheral neuropathy grade >2; ECOG PS 3/4; history of myelodysplastic syndromes/other hematologic malignancies, or solid tumors (Shah 2017). Sites administered pt HRQoL questionnaires and provided clinical data at baseline and quarterly during follow-up until death or study discontinuation. Differences in HRQoL at baseline, changes from baseline to 1 and 2 years, and survival outcomes, adjusted for covariates via propensity score, were compared between RCT-eligible/-ineligible pts.Results: Of the 3011 pts enrolled, 2873 pts met the CRAB (hyperCalcemia, Renal failure, Anemia, and Bone disease) criteria per IMWG at enrollment. Of these, 1622 (56.5%) were identified as RCT-eligible and 1251 (43.5%) as RCT-ineligible (data cut-off February 7, 2019). Both groups were similar in median age, sex, race, and ethnicity distribution, although the RCT-ineligible group had more pts aged ≥75 y (26.3% vs 23.2%) and more pts with ECOG PS 3/4 (6.2% vs none). Overall, 34.5% of RCT-ineligible pts received a transplant vs 42.8% of RCT-eligible pts. More RCT-ineligible pts had ISS stage III disease (39.4% vs 19.8%), elevated calcium (≥11.5 mg/dL; 12.7% vs 6.8%), elevated creatinine (>2.0 mg/dL; 40.3% vs 6.5%), and low hemoglobin (<10 g/dL or >2 g/dL <LLN; 60.8% vs 40.3%). Use of triplet treatment (54.2% vs 56.2%) and alkylator (24.9% vs 20.1%) was similar between the RCT-ineligible/-eligible groups. Lenalidomide + bortezomib + dexamethasone (RVd) was the most common initial therapy, and R was the most common maintenance therapy in both groups, but fewer RCT-ineligible pts received RVd as initial therapy (23.9% vs 31.0%) and R as first maintenance regimen (18.1% vs 22.7%). Absolute baseline HRQoL scores were significantly higher, indicating better HRQoL, in RCT-eligible (115.9) vs -ineligible (111.5) pts on the Functional Assessment of Cancer Therapy-Multiple Myeloma (FACT-MM) Total score (P=0.007), FACT-MM Trial Outcome Index (74.3 vs 70.3, P=0.002), and FACT-MM Subscale (37.3 vs 35.5, P=0.003). Scores were similar for EuroQol-5D Overall Index (0.73 vs 0.72, P=0.5) and Brief Pain Inventory (3.42 vs 3.43, P=0.9). Both RCT-eligible and -ineligible pts showed significant improvement in HRQoL from baseline at years 1 and 2, although the magnitude of improvement was similar between both groups (Fig. 1a and b). RCT-ineligible pts showed significantly shorter median PFS and OS vs RCT-eligible pts (Fig. 2 & 3, respectively).Conclusions: The CONNECT MM registry provided the opportunity to examine key differences between RCT-eligible and -ineligible pts. By applying common RCT eligibility criteria, a substantial proportion of MM pts (43.5%) in this real-world population may have been ineligible to participate in a RCT. RCT-ineligible pts had advanced disease, poor performance status, and poor laboratory parameters at baseline vs RCT-eligible pts, which could affect PFS and OS. These findings enhance our understanding of HRQoL among MM pts, which at present, is largely based on RCT participants. A similar magnitude of HRQoL improvement in both groups at 1 and 2 years suggests the need to evaluate RCT eligibility criteria in MM to help broaden enrollment and maximize external validity.

Duke Scholars

Published In

Blood

DOI

EISSN

1528-0020

ISSN

0006-4971

Publication Date

November 13, 2019

Volume

134

Issue

Supplement_1

Start / End Page

1843 / 1843

Publisher

American Society of Hematology

Related Subject Headings

  • Immunology
  • 3213 Paediatrics
  • 3201 Cardiovascular medicine and haematology
  • 3101 Biochemistry and cell biology
  • 1114 Paediatrics and Reproductive Medicine
  • 1103 Clinical Sciences
  • 1102 Cardiorespiratory Medicine and Haematology
 

Citation

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Wagner, L. I., Toomey, K., Ailawadhi, S., Jagannath, S., Gasparetto, C., Durie, B. G. M., … Abonour, R. (2019). Clinical Outcomes and Health-Related Quality of Life (HRQoL) Among Randomized Clinical Trial (RCT)-Eligible and RCT-Ineligible Patients: Results from the Connect® MM Registry. In Blood (Vol. 134, pp. 1843–1843). American Society of Hematology. https://doi.org/10.1182/blood-2019-126143
Wagner, Lynne I., Kathleen Toomey, Sikander Ailawadhi, Sundar Jagannath, Cristina Gasparetto, Brian G. M. Durie, Mohit Narang, et al. “Clinical Outcomes and Health-Related Quality of Life (HRQoL) Among Randomized Clinical Trial (RCT)-Eligible and RCT-Ineligible Patients: Results from the Connect® MM Registry.” In Blood, 134:1843–1843. American Society of Hematology, 2019. https://doi.org/10.1182/blood-2019-126143.
Wagner LI, Toomey K, Ailawadhi S, Jagannath S, Gasparetto C, Durie BGM, et al. Clinical Outcomes and Health-Related Quality of Life (HRQoL) Among Randomized Clinical Trial (RCT)-Eligible and RCT-Ineligible Patients: Results from the Connect® MM Registry. In: Blood. American Society of Hematology; 2019. p. 1843–1843.
Wagner, Lynne I., et al. “Clinical Outcomes and Health-Related Quality of Life (HRQoL) Among Randomized Clinical Trial (RCT)-Eligible and RCT-Ineligible Patients: Results from the Connect® MM Registry.” Blood, vol. 134, no. Supplement_1, American Society of Hematology, 2019, pp. 1843–1843. Crossref, doi:10.1182/blood-2019-126143.
Wagner LI, Toomey K, Ailawadhi S, Jagannath S, Gasparetto C, Durie BGM, Narang M, Rifkin RM, Terebelo HR, Omel JL, Hardin JW, Lee HC, Srinivasan S, Liu L, Dhalla M, Catamero D, Abonour R. Clinical Outcomes and Health-Related Quality of Life (HRQoL) Among Randomized Clinical Trial (RCT)-Eligible and RCT-Ineligible Patients: Results from the Connect® MM Registry. Blood. American Society of Hematology; 2019. p. 1843–1843.

Published In

Blood

DOI

EISSN

1528-0020

ISSN

0006-4971

Publication Date

November 13, 2019

Volume

134

Issue

Supplement_1

Start / End Page

1843 / 1843

Publisher

American Society of Hematology

Related Subject Headings

  • Immunology
  • 3213 Paediatrics
  • 3201 Cardiovascular medicine and haematology
  • 3101 Biochemistry and cell biology
  • 1114 Paediatrics and Reproductive Medicine
  • 1103 Clinical Sciences
  • 1102 Cardiorespiratory Medicine and Haematology