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3351 Survival Following Quadruplet and Triple Therapy in Transplant in-Eligible Multiple Myeloma - a Meta-Analysis of Recent Clinical Trials

Program: Oral and Poster Abstracts
Session: 653. Multiple Myeloma: Clinical and Epidemiological: Poster II
Hematology Disease Topics & Pathways:
Research, Clinical trials, Epidemiology, Clinical Research, Health outcomes research, Survivorship
Sunday, December 8, 2024, 6:00 PM-8:00 PM

Kuldeepsinh Atodaria, MD1, Keerthi Sripathi, MD2*, Samyukta Varma, MD3*, Tarun Parvataneni, MD4*, Navanita Biswas, MD5*, Bhavya Raja Gopal Yarlagadda, MD6*, Megha Panchal, MBBS7*, Hashwin Pilathodan, MBBS8*, Janani Arunachalam, MBBS9*, Shalin Rawal, MBBS10*, Jujhar Sandhu, MD11* and Urvish Patel, MD12*

1Tower Health Reading Hospital, West Reading, PA
2Arkansas College of Osteopathic Medicine Program, Fort Smith, AR
3Marshfield Clinic, Marshfield, WI
4Aiken Regional Medical Center, Aiken, SC
5Tower Health Reading Hospital, west reading
6MUSC Kershaw medical center, camden
7GMERS Medical College,sola, Odhav, AL, India
8Coimbatore Medical College, coimbatore, India
9University of Connecticut, Farmington, CT
10NYMC st. Mary's General Hospital and Saint Clare's Health, denville
11Ampla Health, yuba
12Icahn School Medicine at Mount Sinai, Jersey City, NJ

INTRODUCTION

In the management of transplant-ineligible multiple myeloma (TIMM), therapeutic strategies are crucial for improving patient outcomes. Recent clinical trials have explored the efficacy of Quadruplet therapy and Triplet therapy in this context. Quadruplet therapy, involving an additional drug, has been proposed to offer enhanced benefits in overall survival and progression-free survival.

AIM

This meta-analysis aimed to evaluate the comparative effectiveness (overall survival [OS] and progression-free survival [PFS]) of Quadruplet vs Triplet therapy in TIMM regimens to inform clinical decision-making and optimize patient care.

METHODS

Type of Study: Meta-analysis of Phase 3 clinical trials

Endpoint: Evaluate OS and PFS in Quadruplet vs Triplet therapy

Search strategy: PRISMA protocol using keywords (("multiple myeloma"[Title/Abstract] AND ("quadruple therapy"[Title/Abstract] OR "triple therapy"[Title/Abstract] OR ("bortezomib-lenalidomide-dexamethasone"[All Fields] AND "VRd"[Title/Abstract]) OR ("lenalidomide-dexamethasone"[All Fields] AND "Rd"[Title/Abstract]) OR ("bortezomib-melphalan-prednisone"[All Fields] AND "VMP"[Title/Abstract]) OR ("CD38-targeted"[All Fields] AND "antibody"[Title/Abstract]))) NOT "Transplant-eligible"[All Fields]) AND ((y_10[Filter]) AND (clinicaltrial[Filter] OR clinicaltrialphasei[Filter] OR clinicaltrialphaseii[Filter] OR clinicaltrialphaseiii[Filter] OR clinicaltrialphaseiv[Filter] OR multicenterstudy[Filter] OR observationalstudy[Filter] OR randomizedcontrolledtrial[Filter]) AND (fft[Filter]) AND (humans[Filter]) AND (english[Filter])) to identify clinical trials from last 10 years.

  • Inclusion criteria: Only Clinical trials recruited TIMM patients in the last 10 years
  • Exclusion criteria: Studies other than clinical trials, non-human, non-English, and non-full text studies were excluded.

Study selection & Data extraction: Using eligibility criteria and keywords, we screened the abstracts and evaluated them for their inclusion in our meta-analysis. From screen abstracts, full-length articles were obtained and studied individually for their eligibility in quantitative analysis (meta-analysis). Data on study name, design, country, duration, sample size, population characteristics [country, mean/median age, sex], type of intervention, and outcomes (OS and PFS) were collected.

Statistical analysis: Review Manager 5.3 software was used to analyze the data. We performed random effects models to estimate the pooled effect size (pooled odds ratio) and 95% confidence interval (95% CI). Forest plots were obtained. p<0.05 was considered statistically significant. Heterogeneity (I2 values) was identified and I2>75% represented high heterogeneity. Risk of bias analysis was performed using the Newcastle-Ottawa Scale.

RESULTS

Out of 51 studies, fulfilling the criteria, nine studies had data on the management of TIMM, of which five studies had data on outcomes of Quadruplet vs Triplet therapy. ALCYONE, IMROZ, and OCTANS were the main multicenter, randomized, and open-label clinical trials covering 160+ sites in 25+ countries. We found 607 patients (of 1196) on Quadruplet and 368 patients (of 1142) on Triplet therapy. Quadruplet therapy had 88% higher odds of OS [OR: 1.88, 95%CI: 1.51-2.35, p<0.00001, I2: 0%] and 178% higher odds of PFS [2.78, 0.83-9.33, p=0.1, I2: 92%] in compared to Triplet therapy. [Pooled OR for survival: 2.30, 1.36-3.87, p=0.002, I2: 0%]. Quadruplet therapy had higher odds of MRD negative [4.04, 2.32-7.03, p<0.00001, I2: 52%] and RR [2.25, 1.66-3.05, p<0.00001, I2: 0%] in compared to Triplet therapy. NOS suggested a moderate risk of bias.

CONCLUSION

In conclusion, our meta-analysis demonstrates that Quadruplet therapy significantly outperforms Triplet therapy in transplant-ineligible multiple myeloma patients, with notable improvements in overall survival and progression-free survival. The Quadruplet regimen also enhances the likelihood of achieving minimal residual disease negativity and a higher response rate. These findings underscore the potential benefits of integrating an additional drug into treatment regimens for better clinical outcomes.

Disclosures: No relevant conflicts of interest to declare.

*signifies non-member of ASH