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Are you thinking deep enough
in early relapsed* or refractory multiple myeloma (RRMM)?

Learn how re-treatment may be associated with patient outcomes

Explore patient outcomes among re‑treated patients with RRMM

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Understand current re-treatment patterns across RRMM in a real-world setting

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Despite advances in therapy, treatment recommendations remain broad, and all patients will eventually relapse

Over the past few years, there have been significant developments in the treatment of multiple myeloma. However, the therapies are not cures, so all patients will eventually relapse. In a recent real-world study, researchers looked to understand the patterns and outcomes for patients who were double-exposed, double-class refractory, and triple-class refractory to therapy.

*NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for multiple myeloma define early relapsed as those occurring with 1-3 prior therapies.
Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Multiple Myeloma V.3.2023. © National Comprehensive Cancer Network, Inc. 2022. All rights reserved. Accessed May 17, 2023. To view the most recent and complete version of the guideline, go online to NCCN.org. NCCN makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way.

Results From a Longitudinal Retrospective Cohort Study of Treatment Patterns in Patients With RRMM

Triple‑class refractory patients had shorter median overall survival (OS), duration of therapy (DoT), and time to next therapy (TTNT) durations from the index date compared with double‑class refractory patients and double‑exposed patients†

Months

Median Survival From Index LoT‡
  • Double-exposed (N=650) 43 Months
  • Double-class refractory (n=381) 22 Months
  • Triple-class refractory (n=173) 12 Months

Months

Median Duration of Therapy
  • Double-exposed (N=650) 5 Months
  • Double-class refractory (n=381) 3 Months
  • Triple-class refractory (n=173) 3 Months

Months

Median Time to Next Therapy
  • Double-exposed (N=650) 7 Months
  • Double-class refractory (n=381) 4 Months
  • Triple-class refractory (n=173) 3 Months

†Results from a longitudinal retrospective cohort study of a subset of the COTA Healthcare de-identified real-world database derived from US electronic health records of partnered healthcare providers from 1988 through Q1 2020. The study included patients (N=650) ≥18 years of age at index date with active RRMM previously exposed to one proteasome inhibitor (PI) and one immunomodulatory agent who had received at least three prior lines of therapy (LoTs). Patients with active RRMM were identified as double-exposed (N=650) if they had previously been exposed to one PI and one immunomodulatory agent. Among these patients, those who were refractory to at least one PI and at least one immunomodulatory agent were classified as double-class refractory patients (n=381), and those who were refractory to at least one PI, immunomodulatory agent, and anti-cluster of differentiation (CD) 38 monoclonal antibody (mAb) (daratumumab) were classified as triple-class refractory patients (n=173). Outcomes measured were overall survival (OS), duration of therapy (DoT), and time to next treatment (TTNT), which were analyzed using Kaplan-Meier survival analysis methods. For the double-exposed cohort, index dates were defined as the date of initiation of the fourth LoT. For the double-class and triple-class refractory cohorts, index dates were defined as the date of initiation of the subsequent LoT after reaching double-class refractory status or triple-class refractory status, respectively. Inclusion criteria differed across cohorts. See full inclusion and exclusion criteria in the study design.

‡Index LoT was defined as the line of therapy initiated on the index date.

CI=confidence interval; D-EXP=double exposed; DR=double refractory; LoT=line of therapy; TR=triple refractory.

Think deeper: does this survival data reflect your clinical experience?

There is no standardized approach to Treating patients with RRMM

Therapy Selection Is Influenced by Multiple Factors, Including§:

  • Individual Patient and
    Disease Characteristics

  • Expected Efficacy/
    Tolerability

  • Patient Response to
    Previous Therapy

  • Number of Prior
    Lines of Therapy

Reuse of Previously Employed Treatments Is Common, Even Those to Which Patients Had Become Refractory§

  • double-exposed 22.5%
  • double-class refractory 24.3%
  • triple-class refractory 39.3%

Disease progression was the most common reason for treatment discontinuation in all cohorts (60%) during index lines of therapy (LoT)

§Results from a longitudinal retrospective cohort study of a subset of the COTA Healthcare de-identified real-world database derived from US electronic health records of partnered healthcare providers from 1988 through Q1 2020. The study included patients (N=650) ≥18 years of age at index date with active RRMM previously exposed to one proteasome inhibitor (PI) and one immunomodulatory agent who had received at least three prior lines of therapy (LoTs). Patients with active RRMM were identified as double-exposed (N=650) if they had previously been exposed to one PI and one immunomodulatory agent. Among these patients, those who were refractory to at least one PI and at least one immunomodulatory agent were classified as double-class refractory patients (n=381), and those who were refractory to at least one PI, immunomodulatory agent, and anti-cluster of differentiation (CD) 38 monoclonal antibody (mAb) (daratumumab) were classified as triple-class refractory patients (n=173). Outcomes measured were overall survival (OS), duration of therapy (DoT), and time to next treatment (TTNT), which were analyzed using Kaplan-Meier survival analysis methods. For the double-exposed cohort, index dates were defined as the date of initiation of the fourth LoT. For the double-class and triple-class refractory cohorts, index dates were defined as the date of initiation of the subsequent LoT after reaching double-class refractory status or triple-class refractory status, respectively. Inclusion criteria differed across cohorts. See full inclusion and exclusion criteria in the study design.

Think deeper: When do you consider it is time to evaluate other options?

As the disease changes, a change in approach may be warranted. Now may be the time to think deeper.

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Wang, et al. STUDY DESIGN1

Wang, et al. was a longitudinal retrospective cohort study. Patients were identified in the COTA Healthcare de‑identified real-world database derived from US electronic health records of partnered healthcare providers from 1988 through Q1 2020.

Study Flow2

* Last data encounter: last date at which the last patient’s last visit was recorded.

† Evidence of clinical activity or record of death was required within a year of the index date.

Patient Types1

Patients were divided into 3 different groups based on their treatment.

Double-exposed patients (N=650)

  • Exposed to a PI and an immunomodulatory agent

Double-class refractory patients (n=381)

  • Double-class refractory, i.e., refractory to a PI and an immunomodulatory agent; and a subsequent therapy receipt
  • This is a subset of the double-exposed population

Triple-class refractory patients (n=173)

  • Triple-class refractory, i.e., refractory to a PI, an immunomodulatory agent, and an anti-CD38 mAb; ≥4 prior LoT and a subsequent therapy receipt
  • This is a subset of the double-class refractory population

Index Dates Differed Across Patient Types2
An index date was established for each patient. The index date was defined differently across patient types.

  • Double-exposed: Initiation date of 4L therapy
  • Double-class Refractory (DCR): Initiation date of the +4L therapy after reaching DCR status
  • Triple-class Refractory (TCR): Initiation of +5L therapy after reaching TCR status

Earliest and Median Index Dates2

  Double-Exposed Double-Class Refractory Triple-Class Refractory
Earliest index date Q4 2003 Q2 2007 Q1 2015
Median index date Q2 2015 Q4 2015 Q2 2017

Establishing the baseline2
The baseline period was defined as 6 months prior to the index date. During the baseline period, researchers looked for evidence of clinical activity. Evidence of clinical activity was required.

Following up2
The follow-up period was defined as the index date through the end of data availability or death. The last encounter date was in Q1 2020. During the follow-up period, researchers looked for evidence of clinical activity and a lack of evidence of clinical trial participation during the index LoT.

INCLUSION CRITERIA2

Patients were included in the study based on the following:

  • Patients with active myeloma
  • Treatment with ≥3 prior LoTs for MM
  • ≥18 years of age as of the index date
  • Evidence of clinical activity (i.e., an encounter*) within the six months prior to the index date (baseline period)
  • Evidence of clinical activity (i.e., an encounter*) or death at any time within the one year following the index date

EXCLUSION CRITERIA2

Patients were excluded from the study based on the following:

  • Receipt of treatment as part of a clinical trial at any point during index LoT†

* An encounter is defined as any clinical record within the COTA database, including laboratory values, procedures or comorbidity assessments.

† Index LoT was defined as the line of therapy initiated on the index date.

4L=fourth line; 5L=fifth line; CD38=cluster of differentiation-38; LoT=line of therapy; mAb=monoclonal antibody; MM=multiple myeloma; PI=proteasome inhibitor.

References: 1. Wang PF, Yee CW, Gorish B, et al. Treatment patterns and overall survival of patients with double-class and triple-class refractory multiple myeloma: a US electronic health record database study. Leuk Lymphoma. 2023;64(2):398-406. doi:10.1080/10428194.2022.2140284 2. Wang PF, Yee CW, Gorish B, et al. Treatment patterns and overall survival of patients with double-class and triple-class refractory multiple myeloma: a US electronic health record database study. Supplement. Leuk Lymphoma. 2023;64(2):398-406. doi:10.1080/10428194.2022.2140284