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Are you thinking deep enough
in relapsed or refractory multiple myeloma?

Learn more about the importance of deep responses in multiple myeloma

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Relapse is expected,
but deep response could be too
1,2

In multiple myeloma, relapse is inevitable due to the genomic evolution that is characteristic of the disease. With each relapse or with the development of refractory disease, fewer patients achieve a deep response to anti-myeloma therapy. In fact, a study showed that the number of patients who achieved a deep response decreased to less than 5% as they progressed through subsequent lines of therapy after being exposed to an immunomodulatory agent, a proteasome inhibitor (PI), and an anti-CD38 monoclonal antibody (mAb).1,2

Diminishing depth of response in patients refractory to an anti-CD38 mAb2*

1006080402090507030100Percentage of patientsFirst lineSecond lineThird line(n=249)(n=158)(n=87)31.3%ORR21.5%ORR25.3%ORRPRVGPRCR/sCR
1006080402090507030100Percentage of patientsFirst lineSecond lineThird line(n=158)(n=87)(n=249)31.3%ORR21.5%ORRPRVGPRCR/sCR25.3%ORR

CR=complete response; mAb=monoclonal antibody; ORR=overall response rate; PI=proteasome inhibitor; PR=partial response; sCR=stringent complete response; VGPR=very good partial response.

*The study included 275 patients with multiple myeloma who were disease refractory to CD38 mAb administered alone or in combination (known as index regimen). Each line of therapy is a subsequent line of therapy, defined as lines of therapy after refractory to anti-CD38 mAb alone or in combination and used in the management of relapsed or refractory multiple myeloma. Alkylator, PI, and daratumumab-based regimens were most commonly used as first subsequent lines of therapies; these groups were not mutually exclusive.2

MAMMOTH Study Design

Learn more about this unmet need across lines of therapy in multiple myeloma

Criteria for defining treatment response and disease status in relapsed or refractory multiple myeloma

The goal of treatment strategies against multiple myeloma is to improve outcomes and prolong patient survival. Criteria such as sCR and CR may be considered one of the strongest prognostic measurements in relapsed or refractory multiple myeloma.1,3,4

Standard IMWG response criteria

International Myeloma Working Group response criteria for multiple myeloma4

CR as clinically defined
+ Normal FLC ratio
+ No clonal cells in BM biopsy by IHC
(κ/λ ratio: ≤4:1 for κ patients or ≥1:2 for λ patients after counting ≥100 plasma cells)

sCR > CR

Negative M-protein IF in serum and urine
+ Disappearance of any soft tissue plasmacytomas
+ <5% PCs in BM aspirates

CR > VGPR

Detectable M-protein IF in serum and urine but not on electrophoresis
or
≥90% reduction in serum M-protein plus urine M-protein level <100 mg per 24 h

VGPR > PR

≥50% ↓ of serum M-protein
+ ≥90% ↓ in 24-h urine M-protein or to <200 mg/24 h
+ ≥50% size ↓ of soft tissue plasmacytomas (if present at baseline)
If serum/urine M-protein unmeasurable: ≥50% ↓ in involved and uninvolved FLC levels difference
If serum/urine M-protein and FLC unmeasurable: ≥50% ↓ in PCs (provided baseline BM PC was ≥30%)

PR > MR

≥25% but ≤49% ↓ of serum M-protein
+ 50%-89% ↓ in 24-h urine M-protein
+ ≥50%↓ in the size of soft tissue plasmacytomas (if present at baseline)

MR > SD

Not meeting criteria for CR, VGPR, PR, MR, or PD

SD > PD

Any ≥1 of the following 4:
25% ↑ from lowest confirmed response value in ≥1 of the following:

  1. Serum M-protein (Abs increase ≥0.5 g/dL or ≥1 g/dL, if lowest M component ≥5 g/dL)
  2. Urine M-protein (Abs increase must be ≥200 mg/24 h). In patients without measurable serum/urine M-protein: differences between involved and uninvolved FLC levels (Abs increase must be >10 mg/dL). In patients without measurable serum and urine M-protein levels and without measurable involved FLC levels, bone marrow plasma-cell percentage irrespective of baseline status (Abs increase must be ≥10%)
  3. Appearance of new lesion(s), ≥50% nadir increase of >1 lesion, or ≥50% increase in longest diameter of previous lesion >1 cm in short axis
  4. ≥50% increase in circulating PCs (min 200 cells/µL)

Abs=absolute; BM=bone marrow; CR=complete response; FLC=free light chain; h=hour; IF=immunofixation; IHC=immunohistochemistry; IMWG=International Myeloma Working Group; MR=minimal response; PC=plasma cell; PD=progressive disease; PR=partial response; sCR=stringent complete response; SD=stable disease; VGPR=very good partial response.

Achievement of sCR or CR is the goal in relapsed or refractory multiple myeloma1,4

Is there a link between depth of response and PFS or OS?

Evidence points to the importance of depth of response in relapsed or refractory multiple myeloma. The data suggest that patients with relapsed or refractory multiple myeloma who achieve a deep response may experience prolonged survival compared with patients who achieve partial response (PR), even after treatment with an immunomodulatory agent, a proteasome inhibitor (PI), and an anti-CD38 mAb.1,2,5

Deep responses may be predictive of longer survival outcomes2

VGPR/CR(n=27)PR(n=51)SD(n=84)PD (n=66)MonthsPFS by depth of response2†Proportion survivingP<0.0010.00.20.40.60.81.00102030
VGPR/CR(n=27)PR(n=51)SD(n=84)PD (n=66)MonthsProportion survivingP<0.001010203040500.00.20.40.60.81.0OS by depth of response2†

CR=complete response; mAb=monoclonal antibody; OS=overall survival; PD=progressive disease; PFS=progression-free survival; PR=partial response; SD=stable disease; VGPR=very good partial response.

The study included 275 patients with multiple myeloma who were disease refractory to CD38 mAb administered alone or in combination (known as index regimen). PFS and OS of patients refractory to CD38 mAb according to depth of response to next line of therapy.2

MAMMOTH Study Design

Median PFS and median OS improved in this study as patients achieved a deeper level of response2‡

Median PFS and median OS chart Median PFS and median OS chart

CR=complete response; mAb=monoclonal antibody; OS=overall survival; PD=progressive disease; PFS=progression-free survival; PR=partial response; SD=stable disease; VGPR=very good partial response.

The study included 275 patients with multiple myeloma who were disease refractory to CD38 mAb administered alone or in combination (known as index regimen).2

The hope is that more patients may achieve a deep response with emerging therapies on the horizon

Sign up today! Learn more about depth of response in relapsed or refractory multiple myeloma

Discover insights about how some measures of deep response may provide better survival outcomes in patients with relapsed or refractory multiple myeloma.

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