2021 IMW carfilzomib combination regimen in the treatment of multiple myeloma

The 18th International Myeloma Symposium (IMW) in 2021 will be held simultaneously in Vienna, Austria and online on September 8-11, 2021.
The conference is hosted by the International Myeloma Society (IMS) and is dedicated to the promotion of multiple myeloma ( MM) and the latest breakthrough scientific and clinical communication on plasma cell diseases
.

The research progress of a number of carfilzomib-related programs in the treatment of MM was announced at this meeting
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The editor now organizes the main content of the research as follows for the reference of readers
.

Abstract OAB-003: Sequential Carfilzomib maintenance treatment in newly diagnosed MM patients receiving ASCT or KCd regimen consolidation treatment: CARDAMON study results Research background Newly diagnosed multiple myeloma (NDMM) patients reached minimal residual disease after induction and consolidation treatment (MRD) is negative, whether it is necessary to receive autologous hematopoietic stem cell transplantation (ASCY) is not yet clear
.

Carfilzomib can replace lenalidomide as a maintenance treatment option for NDMM patients
.

The CARDAMON study explored the efficacy of KCd (carfilzomib, cyclophosphamide, dexamethasone) regimen induction therapy followed by ASCT or KCd regimen consolidation therapy followed by carfilzomib maintenance therapy
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Research Methods The study included NDMM patients receiving 4 cycles of induction therapy with KCd regimen (Carfilzomib: 20/56 mg/m2 every two weeks; cyclophosphamide: 500 mg on days 1, 8, and 15; dexamethasone: weekly 40 mg), followed by a 1:1 random allocation to receive ASCT or 4 cycles of KCd consolidation therapy, followed by 18 cycles of carfilzomib maintenance therapy (56 mg/m2 on days 1, 8, and 15)
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After induction therapy, before maintenance therapy, and 6 months after maintenance therapy, the patient's MRD status (level 10-5) was evaluated by flow cytometry
.

The primary endpoint of the study is to achieve very good partial remission (VGPR) and better remission after induction therapy and 2-year progression-free survival (PFS) rate after randomization.
Secondary endpoints include improvement of disease remission, consolidation therapy or maintenance MRD status changes after treatment
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Results of the study: A total of 281 patients were randomly assigned.
Among them, the median PFS of the ASCT group was not reached, and the median PFS of the consolidation treatment group was 3.
4 years.
Consolidation treatment did not show non-inferiority of efficacy (2-year PFS rate difference) : 6.
5%; 70%CI: 1.
0%-11.
1%)
.

196 patients received carfilzomib maintenance treatment (99 cases in the ASCT group and 97 cases in the consolidation treatment group), and 17 patients were still receiving maintenance treatment
.

At a median follow-up of 15.
9 months (range: 0-21.
5), patients received a median of 16 (range: 1-18) cycles of maintenance therapy
.

Forty-one patients (8 in the ASCT group and 6 in the consolidation treatment group) discontinued maintenance treatment due to the epidemic, and 15 patients (9 in the ASCT group and 6 in the consolidation treatment group) discontinued maintenance treatment
.

The median dose of carfilzomib was 50.
6 mg/m2, and the dose of carfilzomib received by patients in the two groups was similar (51.
2 mg/m2 vs 49.
4 mg/m2; P=0.
03)
.

14.
1% of patients in the ASCT group and 22.
7% of the patients in the consolidation treatment group discontinued carfilzomib due to disease progression, and 7.
1% of the patients in the ASCT group and 4.
1% of the patients in the consolidation treatment group discontinued carfilzomi due to adverse events (AE) Zomi
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The most common AEs were hypertension and infection.
Compared with the consolidation treatment group, patients in the ASCT group had significantly more grade 3 AEs (P=0.
01)
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The proportion of patients or clinicians who voluntarily proposed to withdraw from maintenance therapy was low, but most of them occurred in the ASCT group (9.
1% vs 1%)
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 MRD-negative patients after ASCT or consolidation treatment had significantly longer PFS than MRD-positive patients (P=0.
002), and the MRD-negative rate of patients in the ASCT group was significantly higher (53.
6% vs 35.
1%; P=0.
01)
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After 6 months of maintenance treatment, MRD-negative patients had longer PFS than MRD-positive patients (P=0.
004), and the MRD-negative rate of patients in the ASCT group was also higher after 6 months of maintenance treatment (58.
1% vs 40.
5%; P=0.
02 )
.

27.
8% of MRD-positive patients became MRD-negative after ASCT or consolidation treatment, and the MRD-negative rate of patients in the ASCT group was higher (39.
1% vs 16.
1%; P=0.
004)
.

23.
5% of MRD-positive patients became MRD-negative during maintenance treatment (ASCT group: 30.
6%; consolidation treatment group: 17.
8%; P=0.
2)
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At 6 months of maintenance treatment, the MRD-negative maintenance status of patients in the ASCT group and the consolidation treatment group was similar (P=0.
3)
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There is no evidence that when MRD-negative status is achieved will affect PFS
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The conclusion of the study is that NDMM patients have a good tolerance for maintenance therapy with carfilzomib at 56 mg/m2 per week
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Compared with consolidation therapy, patients receiving ASCT have a higher rate of negative MRD after 6 months of maintenance treatment
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However, patients receiving ASCT also experienced more grade 3 AEs, and more patients discontinued maintenance treatment due to AEs
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Abstract OAB-004: Carfilzomib-based induction and consolidation treatment program followed by lenalidomide monotherapy or combined with carfilzomib for maintenance treatment of high-risk MM patients: FORTE study results, research background and standard cytogenetic risk MM patients In contrast, patients with high-risk cytogenetics have a worse prognosis
.

The FORTE study showed that compared with the standard KRd regimen (carfilzomib, lenalidomide, dexamethasone; KRd12) and the KCd regimen sequential ASCT (KCd-ASCT), the KRd regimen sequential ASCT (KRd-ASCT) can Significantly improve the PFS of MM patients
.

This study evaluated the impact of related treatment options on PFS in high-risk MM patients
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Research methods The study included patients randomly assigned to receive KRd-ASCT, KCd-ASCT, and KRd12 regimens, and then randomly assigned to receive carfilzomib combined with lenalidomide or lenalidomide as maintenance therapy
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High-risk patients are defined as having ≥1 high-risk features (del(17p), t(4;14), t(14;16), del(1p), gain(1q), amp(1q)), double-hit patient definition For the presence of ≥ 2 high-risk features, patients without high-risk features are standard-risk patients
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Results of the study A total of 474 patients were included in the study, of which 396 patients completed the FISH test
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243 patients are high-risk patients, 105 patients are double-hit patients, and 153 patients are standard-risk patients
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Among high-risk patients, 60 patients have del(17p), 65 patients have t(4;14), 20 patients have t(14;16), 44 patients have del(1p), and 126 patients have gain(1q ), 49 patients have amp(1q)
.

 For standard-risk patients (4-year PFS rate: 80%, 67%, 57%), high-risk patients (4-year PFS rate: 62%, 45%, 45%), double-strike patients (4-year PFS rate: 55%, 31%, 33%), the KRd-ASCT scheme improved PFS compared to the KRd12 scheme and the KCd-ASCT scheme
.

Although the number of patients in each subgroup is limited, they have del(17p) (HR: 0.
61; P=0.
3), t(4;14) (HR: 0.
59; P=0.
2), gain(1q) (HR: 0.
45; P=0.
02) FPS benefit from KRd-ASCT regimen and KRd12 regimen was observed in patients
.

In patients with del(1p), the KRd-ASCT regimen (HR: 0.
24; P=0.
06) and the KRd12 regimen (HR: 0.
33; P=0.
09) showed better efficacy benefits than the KCd-ASCT regimen
.

Regardless of the treatment regimen, patients with amp(1q) have the worst prognosis
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 Compared with lenalidomide single-agent maintenance treatment, carfilzomib combined with lenalidomide maintenance treatment program improved standard-risk patients (3-year PFS rate: 90% vs 73%; HR: 0.
42; P=0.
06), High-risk patients (3-year PFS rate: 69% vs 56%; HR: 0.
6; P=0.
04), double-hit patients (3-year PFS rate: 67% vs 42%; HR: 0.
53; P=0.
1) PFS
.

Although the number of patients in the subgroup is limited, there are del(17p) (HR: 0.
59; P=0.
37), t(4;14) (HR: 0.
59; P=0.
3), gain(1q) (HR: 0.
54; P =0.
07), del(1p) (HR: 0.
23; P=0.
08) patients were observed to benefit from the efficacy of carfilzomib combined with lenalidomide maintenance therapy, while patients with amp(1q) no matter what they received None of these maintenance treatment programs benefited (HR: 0.
83; P=0.
7)
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Research conclusions KRd-ASCT regimen and maintenance therapy of carfilzomib combined with lenalidomide are effective for standard-risk, high-risk, and double-strike MM patients
.

Even for patients with high-risk cytogenetics, the KRd-ASCT regimen (4-year PFS rate: 62% of high-risk patients, 55% of double-strike patients) and the maintenance treatment regimen of carfilzomib combined with lenalidomide (3-year PFS rate: 69% of high-risk patients and 67% of double-strike patients) can still bring PFS benefits, providing effective treatment options for MM patients with unmet need for treatment
.

Reference source: 1.
Rakesh Popat, et al.
2021 IMW.
OAB-003.
2.
Roberto Mina, et al.
2021 IMW.
OAB-004.
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