RANDOMIZED CLINICAL TRIAL (RCT) REPRESENTATIVENESS & OUTCOMES IN RELAPSED/REFRACTORY MULTIPLE MYELOMA (RRMM) REAL WORLD (RW) PATIENTS: COMPARISON OF ASPIRE, TOURMALINE-MM1, POLLUX, & ELOQUENT RCTS
Author(s): ,
Ajai Chari
Affiliations:
Icahn School of Medicine at Mount Sinai,New York,United States
,
Dorothy Romanus
Affiliations:
Millennium Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited,Cambridge,United States
,
Eileen Farrelly
Affiliations:
Xcenda, LLC,Palm Harbor,United States
,
Hui Huang
Affiliations:
Millennium Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited,Cambridge,United States
,
Marlo Blazer
Affiliations:
Xcenda, LLC,Palm Harbor,United States
,
Aditya Raju
Affiliations:
Xcenda, LLC,Palm Harbor,United States
,
Stephen Noga
Affiliations:
Millennium Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited,Cambridge,United States
Paul Richardson
Affiliations:
Dana Farber Cancer Institute,Boston,United States
EHA Library. Romanus D. 06/16/18; 215636; PS1336
Dr. Dorothy Romanus
Dr. Dorothy Romanus
Contributions
Abstract

Abstract: PS1336

Type: Poster Presentation

Presentation during EHA23: On Saturday, June 16, 2018 from 17:30 - 19:00

Location: Poster area

Background
Only 3% of patients (pts) participate in oncology trials in the United States (US).1 Strict eligibility criteria and high enrolment ex-US limit the generalizability of trial results and applicability of the benefit/risk treatment profile to RW pts.2

Aims
To estimate the proportion of US RW pts who are representative of eligibility criteria in recently completed trials of triplet lenalidomide/dexamethasone (Rd)-based regimens in RRMM and to compare the baseline characteristics and overall survival (OS) between RCT-eligible and RCT-ineligible pts within each trial group. 

Methods

RRMM pts were followed retrospectively in a large US electronic health record (EHR) database.3  Included were pts initiating treatments consistent with either the experimental or control regimen in 2nd-4th line of therapy (LOT) based on 4 RCTs: 2 proteasome inhibitor-based (PI) (ASPIRE; TOURMALINE-MM1) and 2 monoclonal antibody-based (mAb) triplet regimens with an Rd backbone (POLLUX; ELOQUENT). RW pts were categorized into “RCT-elig” vs “RCT-inelig” based on whether eligibility criteria for each of the 4 trials in RRMM were met vs not. Unadjusted Cox PH models were performed to estimate OS from start of the index regimen to death between RCT-elig vs RCT-inelig pts in each trial group. Observations were censored at time of loss to follow up/end of study period (6/2017).

Results
Applying the individual trial criteria, 25% (ASPIRE), 35% (TOURMALINE), 41% (ELOQUENT), and 47% (POLLUX) US RW pts met the eligibility criteria. In addition to exclusion criteria related to prior treatment history of/refractory status to an immunomodulatory drug (21% [ELOQUENT], 8% [other trials] of RCT-inelig pts), the most common reasons for ineligibility across trial groups were: low creatinine clearance (27% [ASPIRE]; 9% [other trials]) and other cancer diagnoses (12% [all trials]). Refractory status to a PI as an exclusion criterion in the PI-based trials applied to 54% of ASPIRE & TOURMALINE RCT-inelig pts. Less than 1% of pts were RCT-inelig using the POLLUX & ELOQUENT mAb-based trial criterion of prior exposure to a mAb. Clinically relevant recent cardiovascular comorbidities accounted for 12% (ASPIRE), 9.2% (TOURMALINE), 9.0% (ELOQUENT), and 5.9% (POLLUX) RCT-inelig pts. RW pts who were RCT-elig were generally significantly younger, treated in earlier LOT, more likely to have a history of stem-cell transplant, had a lower comorbidity burden. A lower proportion also had known ISS III disease vs RCT-inelig pts (Table). Except in the ELOQUENT group, the 3-year OS was significantly higher among RCT-elig v RCT-inelig pts but the difference in OS varied across trial groups: 77% v 57% (ASPIRE, P<0.001), 75% v 60% (TOURMALINE, P<0.001), 70% v 63% (POLLUX, P<0.01) and 67% v 65% (ELOQUENT, P=0.16) (Table).

Conclusion
53-75% of RW US pts do not meet eligibility criteria of recently completed trials of novel-triplet regimens in RRMM in large part due to refractoriness to lenalidomide and also PIs, for the PI containing studies. Importantly, OS between RCT-elig vs RCT-inelig pts varied based on trial eligibility characteristics. A limitation of the data is that treatment refractory disease was defined using a proxy4 and may overestimate the true proportion of ineligible pts. Future work will evaluate the impact of individual eligibility criteria on OS.      

Session topic: 14. Myeloma and other monoclonal gammopathies - Clinical

Keyword(s): Myeloma, Relapse, Treatment

Abstract: PS1336

Type: Poster Presentation

Presentation during EHA23: On Saturday, June 16, 2018 from 17:30 - 19:00

Location: Poster area

Background
Only 3% of patients (pts) participate in oncology trials in the United States (US).1 Strict eligibility criteria and high enrolment ex-US limit the generalizability of trial results and applicability of the benefit/risk treatment profile to RW pts.2

Aims
To estimate the proportion of US RW pts who are representative of eligibility criteria in recently completed trials of triplet lenalidomide/dexamethasone (Rd)-based regimens in RRMM and to compare the baseline characteristics and overall survival (OS) between RCT-eligible and RCT-ineligible pts within each trial group. 

Methods

RRMM pts were followed retrospectively in a large US electronic health record (EHR) database.3  Included were pts initiating treatments consistent with either the experimental or control regimen in 2nd-4th line of therapy (LOT) based on 4 RCTs: 2 proteasome inhibitor-based (PI) (ASPIRE; TOURMALINE-MM1) and 2 monoclonal antibody-based (mAb) triplet regimens with an Rd backbone (POLLUX; ELOQUENT). RW pts were categorized into “RCT-elig” vs “RCT-inelig” based on whether eligibility criteria for each of the 4 trials in RRMM were met vs not. Unadjusted Cox PH models were performed to estimate OS from start of the index regimen to death between RCT-elig vs RCT-inelig pts in each trial group. Observations were censored at time of loss to follow up/end of study period (6/2017).

Results
Applying the individual trial criteria, 25% (ASPIRE), 35% (TOURMALINE), 41% (ELOQUENT), and 47% (POLLUX) US RW pts met the eligibility criteria. In addition to exclusion criteria related to prior treatment history of/refractory status to an immunomodulatory drug (21% [ELOQUENT], 8% [other trials] of RCT-inelig pts), the most common reasons for ineligibility across trial groups were: low creatinine clearance (27% [ASPIRE]; 9% [other trials]) and other cancer diagnoses (12% [all trials]). Refractory status to a PI as an exclusion criterion in the PI-based trials applied to 54% of ASPIRE & TOURMALINE RCT-inelig pts. Less than 1% of pts were RCT-inelig using the POLLUX & ELOQUENT mAb-based trial criterion of prior exposure to a mAb. Clinically relevant recent cardiovascular comorbidities accounted for 12% (ASPIRE), 9.2% (TOURMALINE), 9.0% (ELOQUENT), and 5.9% (POLLUX) RCT-inelig pts. RW pts who were RCT-elig were generally significantly younger, treated in earlier LOT, more likely to have a history of stem-cell transplant, had a lower comorbidity burden. A lower proportion also had known ISS III disease vs RCT-inelig pts (Table). Except in the ELOQUENT group, the 3-year OS was significantly higher among RCT-elig v RCT-inelig pts but the difference in OS varied across trial groups: 77% v 57% (ASPIRE, P<0.001), 75% v 60% (TOURMALINE, P<0.001), 70% v 63% (POLLUX, P<0.01) and 67% v 65% (ELOQUENT, P=0.16) (Table).

Conclusion
53-75% of RW US pts do not meet eligibility criteria of recently completed trials of novel-triplet regimens in RRMM in large part due to refractoriness to lenalidomide and also PIs, for the PI containing studies. Importantly, OS between RCT-elig vs RCT-inelig pts varied based on trial eligibility characteristics. A limitation of the data is that treatment refractory disease was defined using a proxy4 and may overestimate the true proportion of ineligible pts. Future work will evaluate the impact of individual eligibility criteria on OS.      

Session topic: 14. Myeloma and other monoclonal gammopathies - Clinical

Keyword(s): Myeloma, Relapse, Treatment

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