2021 ASCO prospective initial treatment of multiple myeloma consolidation treatment plan exploration

The 2021 American Society of Clinical Oncology (ASCO) annual meeting will be held in the near future, and a number of studies will be announced at the meeting to explore the options for consolidating treatment options for newly treated (ND) multiple myeloma (MM).

The editor now organizes the main content of the research as follows for the reference of readers.

Abstract 8000: A comparative study on the efficacy of carfilzomib, cyclophosphamide, dexamethasone consolidation therapy and autologous hematopoietic stem cell transplantation in newly diagnosed MM patients Background NDMM patients usually get higher minimal residual after induction therapy and consolidation therapy The negative rate of MRD, whether these patients need autologous hematopoietic stem cell transplantation (ASCT) remains to be evaluated.

Although the results of some phase III studies support these patients to receive ASCT, the patients in these studies were treated with lenalidomide for maintenance treatment, which improved the prognosis of standard-risk (SR) patients.

The CARDAMON study used carfilzomib-based regimens for induction and maintenance therapy to explore the necessity of ASCT in NDMM patients.

Research method The study included NDMM patients first received 4 cycles of KCd regimen (Carfilzomib: 20/56mg/m2 every two weeks, cyclophosphamide: 500mg, on the first, eighth, and fifteenth days of each treatment cycle, dexamethasone Methosone: 40mg per week) induction therapy, and then randomized to receive ASCT or 4 cycles of KCd consolidation therapy at a ratio of 1:1.
All patients will then receive carfilzomib maintenance therapy for 18 months (56mg/m2, Days 1, 8, and 15 of each treatment cycle).

In the study, the MRD status (10-5 level) of patients was assessed by flow cytometry after induction therapy, before maintenance therapy, and 6 months of maintenance therapy.

The primary endpoints of the study were ≥very good partial response (VGPR) after induction therapy and 2-year progression-free survival (PFS) after randomization.

Research results The study included 281 patients with a median age of 59 years (range: 33-74), of which 24% were high-risk patients [with t(4;14), t(14;16), t(4; 20) or del(17p)].

After induction therapy, 58.
5% of patients achieved ≥VGPR, and the overall remission rate (ORR) was 87%.
The remission of high-risk patients was similar to that of SR patients.

52 patients in the study did not undergo stem cell collection (6 cases of mild remission, 16 cases of disease progression, 19 cases of adverse reactions, 4 cases of death, 3 cases of infection, 1 case of cardiac event, 7 cases of other causes), and 109 patients were randomly assigned Undergoing ASCT, 109 patients were randomly assigned to receive KCd consolidation therapy.

Ninety-nine patients (90.
8%) completed 4 cycles of KCd consolidation therapy, with a median dose of 55.
5 mg/m2, and 104 (95.
4%) patients received ASCT.

78.
5% of patients in the KCd group obtained ≥VGPR after consolidation treatment, and the ≥VGPR rate of patients receiving ASCT was 80.
0% (P=0.
8).

 After 2.
6 years of follow-up, the median PFS of the ASCT group was not reached, and the median PFS of the KCd group was 3.
8 years (HR: 0.
82; 70%CI: 0.
65-1.
05; P=0.
4).

The 2-year PFS rates of ASCT group and KCd group were 75.
5% and 70.
7%, respectively.

Regardless of the randomization, the overall prognosis of high-risk patients is worse than that of SR patients (ASCT group 2-year PFS rate: 52% vs 82%, HR: 4.
09; KCd group 2-year PFS rate: 48% vs 77%, HR: 2.
83) .

There was no significant difference in the 2-year PFS between high-risk patients and SR patients due to randomization.
The 2-year PFS rates of SR patients in the two groups were 82% (ASCT) and 77% (KCd) (HR: 1.
29), respectively.
High-risk patients The 2-year PFS rates were 52% (ASCT) and 48% (KCd) (HR: 1.
06).

In the study, the MRD negative rate of patients after induction therapy was 24.
3%, and the MRD status of high-risk patients and SR patients were similar.

Regardless of the cytogenetic risk, the MRD negative rate of patients receiving ASCT was significantly higher than that of patients receiving consolidation therapy (53.
1% vs 35.
8%; P=0.
02).

Adverse events of grade ≥3 that occurred during the induction treatment included infection (18.
7%), hypertension (11.
2%), anemia (10.
4%), heart disease (3.
6%), vomiting (2.
2%), fatigue (2.
2%), Diarrhea (1.
8%).

Research conclusions For NDMM patients who received KCd regimen induction therapy and carfilzomi single-agent consolidation therapy, KCd regimen consolidation therapy showed no inferior efficacy to ASCT.

Whether receiving ASCT or not, the prognosis of high-risk NDMM patients is poor.

Abstract 8002: Carfilzomib-based induction or consolidation treatment plan followed by ASCT in the treatment of high-risk MM patients has achieved considerable efficacy.

Research background Cytogenetic abnormality (CA) is one of the most important prognostic factors of MM.

The results of the FORTE study showed that the KRd regimen (carfilzomib, lenalidomide, dexamethasone) after the induction or consolidation treatment of sequential ASCT (KRd_ASCT) compared with the KCd regimen sequential ASCT (KCd_ASCT) and non-sequential ASCT The KRd program significantly improved the PFS of MM patients (HR: 0.
53).

At the same time, compared with lenalidomide single-agent maintenance therapy, the maintenance treatment plan of carfilzomib combined with lenalidomide (KR) also significantly improved the PFS of MM patients (HR: 0.
63).

Research methods The study included MM patients randomly assigned to receive KRd_ASCT, KCd_ASCT, 12 cycles of KRd regimen (KRd12) induction or consolidation therapy, and then received KR regimen or lenalidomide single-agent regimen maintenance treatment.

Subgroup analysis assessed each single high-risk (HiR) CA[del(17p), t(4;14), t(4;16), del(1p), and gain(1q) (copy number = 3) The impact of amp(1q) (≥4 copies)] on the prognosis.

Patients with ≥1 HiR CA are defined as HiR patients, patients with ≥2 HiR CAs are defined as double-hit (DH) patients, and patients without HiR CA are defined as SR patients.

The main purpose of the study is to evaluate the impact of patients' disease risk on PFS.

Results of the study A total of 474 patients were included in the study, of which 396 patients received FISH testing (243 HiR, 105 DH, and 153 SR).

Among HiR patients, 60 patients had del(17p), 65 patients had t(4;14), 20 patients had t(4;16), 44 patients had del(1p), and 126 patients had gain(1q).
), 49 patients have amp(1q).

Compared with the KRd12 regimen and the KCd_ASCT regimen, SR patients benefited more after receiving the KRd_ASCT regimen.
The 4-year PFS rate was 67%, 57%, and 80%, respectively.

Compared with KRd12 and KCd_ASCT in HiR patients, the KRd_ASCT regimen also improved the patients' PFS.
The 4-year PFS rate was 62%, 45%, and 45%, respectively.

The efficacy advantages of the KRd_ASCT regimen compared with the KRd12 regimen and the KCd_ASCT regimen were also observed in DH patients.
The 4-year PFS rate was 55%, 31%, and 33%, respectively.

 Although the number of patients in each CA subgroup in the subgroup analysis is small, there are 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) PFS benefit of KRd_ASCT program was better than KRd12 program was observed in patients with (HR: 0.
45; P=0.
02).

The benefits of KRd_ASCT and KRd12 were superior to KCd_ASCT in patients with del(1p).

Regardless of the treatment plan, patients with amp(1q) have a relatively poor prognosis.

Compared with the lenalidomide single-agent regimen, the KR regimen is used in SR patients (3-year PFS: 90% vs 73%; HR: 0.
42; P=0.
06) and HiR patients (3-year PFS: 69% vs 56%; HR : 0.
6; P=0.
04) and DH patients (3-year PFS: 67% vs 42%; HR: 0.
53; P=0.
1) improved PFS.

Although the number of patients in each subgroup is small, 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) observed the benefit of KR regimen over lenalidomide single-drug regimen, while patients with amp(1q) received no matter what The prognosis of these maintenance treatment programs was relatively poor (HR: 0.
83; P=0.
7).

Research conclusions KRd_ASCT scheme and KR scheme are more effective in SR patients, and also bring better PFS benefits for HiR patients and DH patients (KRd_ASCT scheme 4-year PFS rate: HiR: 62%, DH: 55%; KR scheme PFS rate of 3 years after maintenance treatment: HiR: 69%, DH: 67%).

The results of this study support the use of the KRd_ASCT regimen and the KR regimen for HiR patients with unmet need for treatment.

Reference source: 1.
Kwee Yong, et al.
Upfront autologous stem cell transplantation (ASCT) versus carfilzomibcyclophosphamide-dexamethasone (KCd) consolidation with K maintenance in transplant-eligible, newly diagnosed (NDTE) multiple myeloma (MM).
2021 ASCO Annual Meeting .
Abstract 8000.
2.
Francesca Gay, et al.
Carfilzomib-based induction/consolidation with or without autologous transplant (ASCT) followed by lenalidomide (R) or carfilzomib-lenalidomide (KR) maintenance: Efficacy in high-risk patients.
2021 ASCO Annual Meeting .
Abstract 8002.
Poke "read the original text", we make progress together