Plasma Cell Dyscrasias

Dr. Peter Anglin – Stronach Regional Cancer Centre

About Speaker

Dr. Peter Anglin – Stronach Regional Cancer Centre

Dr. Peter Anglin obtained his medical degree from Queen’s University at Kingston and followed this with clinical fellowships in internal medicine, hematology and oncology. He has been in clinical practice for the last 21 years in the Greater Toronto Area and is currently a staff Hematologist/Medical Oncologist and Physician Lead at the Stronach Regional Cancer Centre at Southlake Health in Newmarket, Ontario. Dr. Anglin’s clinical focus has been in hematologic and lymphoid malignancies. After pursuing an MBA from the Rotman School of Management (University of Toronto) he has developed an interest in health systems delivery and process redesign in the clinical ambulatory setting.

MM and AL Amyloid Highlights from ASCO and EHA 2021

Carfilzomib-based induction/consolidation with or without autologous transplant (ASCT) followed by lenalidomide (R) or carfilzomib-lenalidomide (KR) maintenance: Efficacy in high-risk patients. (FORTE Trial)

ASCO 2021 Abstract 8002. Gay et al.
EHA 2021 Abstract S182. Mina et al.

Results Highlights:

  • KRd with ASCT (_ASCT) significantly prolonged PFS vs. KRd12 and KCd_ASCT
    • Standard risk patients benefited from intensification with KRd_ASCT vs KRd12 (HR 0.47, p = 0.05) and KCd_ASCT (HR 0.38, p = 0.01), with a 4-year PFS of 80%, 67% and 57%, respectively.
    • In high-risk patients, KRd_ASCT improved PFS vs KRd12 (HR 0.6, p = 0.04) and KCd_ASCT (HR 0.57, p = 0.01), with a 4-year PFS of 62%, 45% and 45%, respectively.
    • The advantage with KRd_ASCT vs KRd12 (HR 0.53, p = 0.07) and KCd_ASCT (HR 0.49; p = 0.03) was also observed in DH pts (4-year PFS 55%, 31% and 33%, respectively).
  • KRd_ASCT increased the 1-year sustained MRD negativity vs. KRd12 in patients with both high risk (50% vs. 39%) and double hit (47% vs. 25%) MM.

Key Takeaway:

These results support the use of KRd with ASCT in high risk patients, who represent an unmet medical need.

Daratumumab (DARA) Maintenance Vs Observation in Patients With Newly Diagnosed Multiple Myeloma Treated With Bortezomib, Thalidomide, And Dexamethasone ± Daratumumab And ASCT: CASSIOPEIA Part 2 Results

ASCO 2021 Abstract 8004. Moreau and Sonneveld.
EHA 2021 Abstract S180. Moreau et al.

Results Highlights:

  • Median PFS was not reached with daratumumab vs 46.7 months for OBS (median follow up, 35.4 months; hazard ratio [HR] 0.53 [95% CI 0.42–0.68]; P<0.0001).
    • PFS advantage consistent across most subgroups, except for a significant interaction with induction/consolidation treatment arm (P<0.0001; prespecified analysis).
  • Patients who received daratumumab maintenance achieved ≥CR (60.8% vs 72.9%; odds ratio [OR] 2.17 [1.54–3.07]; P<0.0001).
    • In patients with ≥CR at 10−5, the MRD negativity rate was 58.6% with daratumumab maintenance vs 47.1% with OBS (OR 1.80 [1.33–2.43]; P=0.0001)
  • Median OS was not reached in either arm
  • No new safety signals were observed

Key Takeaway:

DARA significantly increased deeper response and MRD negativity rates vs OBS and was well tolerated. Longer follow-up is needed for PFS2 and OS.

Overall Survival Results With Daratumumab, Lenalidomide, And Dexamethasone Versus Lenalidomide And Dexamethasone In Transplant-Ineligible Newly Diagnosed Multiple Myeloma: Phase 3 MAIA Study

EHA 2021 LB1901. Facon et al.

Results Highlights:

  • 5-year OS 66.3% with DRd vs 53.1% Rd (Figure A) and median PFS NR with DRD vs 34.4 mo in Rd arm
  • No new safety signals were observed

Key Takeaway:

After almost 5 years of follow-up, a significant and clinically meaningful OS improvement was demonstrated with the use of D-Rd versus Rd in patients with NDMM who are transplant ineligible, representing a 32% reduction in the risk of death. These results, together with the OS benefit observed in ALCYONE, support the use of frontline DARA-based combination regimens to maximize PFS for optimal long-term outcomes.

Isatuximab plus carfilzomib and dexamethasone versus carfilzomib and dexamethasone in elderly patients with relapsed multiple myeloma: IKEMA subgroup analysis.

ASCO 2021 Abstract 8026. Facon et al.

Results Highlights:

  • The addition of Isa to Kd improved PFS and quality of response in elderly pts, with a manageable safety profile, consistent with the benefit observed in the overall IKEMA study population. (figure)

Key Takeaway:

Isa-Kd provides a potential new treatment option for elderly pts with RMM.

ICARIA-MM: Second Interim Analysis of Phase III Study of Addition of Isatuximab to Pomalidomide and Low-Dose Dexamethasone in R/R Myeloma.

ASCO 2021 Abstract 8016. Richardson et al.

Results Highlights:

  • the overall safety profile remains unchanged from prior analyses.

Key Takeaway:

Isa-Pd demonstrates a significant improvement in TTNT and PFS2 compared with Pd. A strong trend in OS benefit was also seen in the Isa-Pd arm.

Other Key MM News from 2021
  • A number of newer therapies target BCMA have shown promising results. Trials/agents of interest include:
    • ASCO 2021 Abstract 8006. Efficacy and safety of elranatamab (PF-06863135), a B-cell maturation antigen (BCMA)-CD3 bispecific antibody, in patients with relapsed or refractory multiple myeloma (MM). Bahlis et al.
    • ASCO 2021 Abstract 8005. Ciltacabtagene autoleucel, a B-cell maturation antigen (BCMA)-directed chimeric antigen receptor T-cell (CAR-T) therapy, in relapsed/refractory multiple myeloma (R/R MM): Updated results from CARTITUDE-1 (median 18 months FU). Usmani et al.
    • ASCO 2021 Abstract 8016. Updated Findings From the Phase II KarMMa Study of Idecabtagene Vicleucel for R/R Multiple Myeloma. Richardson et al.
  • Trials are looking at moving CAR-T earlier in MM algorithm especially in HR patients (Usmani, ASCO Educational Session 2021)
    • CAR-T therapy for MM in Canada limited to few study centres
    • Ide-cel (Abecma) has NOC indication in Canada
    • Cilta-cel does not have NOC in Canada
Subcutaneous daratumumab + bortezomib, cyclophosphamide, and dexamethasone (VCd) in patients with newly diagnosed light chain (AL) amyloidosis: Updated results from the phase 3 ANDROMEDA study

ASCO 2021 Abstract 8003. Kastritis et al.

Results Highlights:

  • Overall hematologic CR rate continued to be higher with DARA-VCd than VCd (59% vs 19%; odds ratio [OR] 5.9; 95% CI 3.7–9.4; P< 0.0001).
  • More patients achieved a very good partial response or better (≥VGPR) with DARA-VCd than VCd (79% vs 50%; OR 3.7; 95% CI 2.4–5.9; P< 0.0001).
  • Cardiac response rates were higher with DARA-VCd than VCd at 6 mo (42% vs 22%) and at 12 mo (57% vs 28%); renal response rates were 54% vs 27% at 6 mo and 57% vs 27% at 12 mo

Key Takeaway:

Updated results from the ANDROMEDA study reinforce the clinical superiority of DARA-VCd over VCd in pts with newly diagnosed AL amyloidosis.

Hematologic CR must be goal of therapy (correlates with organ response). Access to daratumumab at present 3rd party payer and survival data may be needed for funders. Early data is promising

Thank you to our CARE™ at ASCO/EHA Sponsors