IMS 2022 Voice of China Prof. Gang An's team: Induction therapy for multiple myeloma and advances related to autologous hematopoietic stem cell transplantation

The 19th International Myeloma Society (IMS) Annual Meeting, held August 25-27, 2022 in Los Angeles, USA, is hosted by IMS and is dedicated to promoting the latest breakthrough scientific and clinical exchanges for multiple myeloma (MM) and related plasma cell diseases

Cytogenetic abnormalities (CAs) detected by iFISH are the basis for

Figure 1

The results showed that 118 (43.

Figure 2

iFISH-positive + flow-MRD-negative patients achieved a deeper response compared to iFISH-negative + flow-MRD-positive patients, but this result did not translate into survival benefit regardless of the depth of the response or treatment regimen (Figure 3

Figure 3

The MRD-positive rate of iFISH-positive + flow-MRD-negative patients was higher than that of iFISH-negative + flow-MRD-negative patients (43.

The VRD regimen is considered to be the first-line induction therapy regimen for current NDMM patients
.

But real-world data on VRD solutions in China is not yet perfect
.

Based on this, Professor An Gang's team conducted a retrospective analysis of the efficacy and long-term prognosis of VRD in 87 patients
with NDMM.

The results showed that after 2 courses of induction therapy, the patient's overall response rate (ORR) was 95.
9%, the ≥ complete response (CR) rate was 13.
5%, and the ≥ very good partial response (VGPR) rate was 51.
3%.


After 4 courses of induction therapy, the patient's ORR was 95.
2%, the ≥ CR rate was 46.
0%, and the ≥ VGPR rate was 77.
7%.

Patients are divided into transplant and non-transplant groups according to the treatment
.

In the transplant group, the ≥ VGPR rate (88.
8% vs 97.
2%, P=0.
174), ≥ CR rate (55.
5% vs 77.
2%, P=0.
055) and MRD negative rate (44.
4% vs 77.
8%, P=0.
004) were improved
compared with post-induction therapy.

After induction therapy≥ patients in the non-transplant group had a VGPR rate of 74.
2%, a ≥ CR rate of 35.
5%, and an MRD negative rate of 37.
0%.


Compared with the non-transplanted group, patients in the transplant group had a higher response rate and a lower MRD positivity rate (78.
4% vs 55.
2%, P=0.
045).


The median follow-up was 26.
3 months, and the median progression-free survival (PFS) and overall survival (OS) were not achieved, and the 3-year PFS rate and OS rate were 78.
4% and 87.
1%,
respectively.

The results of the study show that VRD protocols also have good efficacy and significant survival benefits
in the real world.

With the application of new drugs, more and more MM patients are getting MRD negative after early induction therapy
.

In this case, is ASCT still valuable in improving prognosis for mm patients? Professor An Gang's team explored
this.

The results showed that the prognosis of patients with MRD-negative + ASCT was significantly better than that of MRD-negative + non-ASCT group, MRD-positive + ASCT group, and MRD-positive + non-ASCT group (median PFS: 88.
3 months vs 46.
0/42.
8/22.
7 months; Median OS: 90.
6 months vs 76.
4/78.
8/52.
3 months).

Patients were divided into 0HRCA, 1HRCA, and 2+ HRCA groups
based on the number of high-risk cytogenetic abnormalities (HRCA).

In MRD-negative patients, in the 1HRCA group, the 2+ HRCA group, and the R-ISS stage III, patients who underwent ASCT had longer PFS than those
who did not.

In addition, patients with ASCT were observed only in the 2+ HRCA group and in patients with stage III R-ISS with longer OS than those
who did not.

In MRD-negative patients, the DURATION of MRD-negative was significantly longer in the ASCT group than in the non-ASCT group (median duration: 58.
1 months vs 33.
5 months, P=0.
000).


MrD-negative duration was ≥ 2 years in 89.
1% of patients in the ASCT group, compared with 49.
1%
in the non-ASCT group.

Further analysis of different HRCA subgroups showed that ASCT mainly increased the ≥ 2-year MRD-negative persistence rate
in patients in the 1HRCA group (90.
6% vs 38.
9%, P=0.
000) and 2+HRCA group (88.
2% vs 35.
3%, P=0.
001).

In addition, patients with MRD-negative duration ≥2 years had a better prognosis than patients with MRD-negative duration < 2 years
.

Univariate and multivariate influence analysis showed that ASCT was an independent factor influencing the duration of MRD negative (HR: 0.
30, 95% CI: 0.
16-0.
56, P=0.
000).

The above results show that in the era of new drugs, ASCT is necessary
in MRD-negative patients after early induction therapy, especially in patients with HRCA or R-ISS stage III.

The duration of MRD negative is a more important prognostic factor for patients with MM than MRD-negative, while ASCT is an independent factor
influencing the duration of MRD-negative.

ASCT is the standard of care for transplant-eligible PATIENTS WITH MM (TEMM), but there are currently no randomized trials evaluating the optimal number of induction cycles or ideal depth
of remission before ASCT.

In the absence of CR, it is controversial
whether tumor plasma cells will appear in the stem cell collection (SCC) before ascertainment and have a negative impact on the survival of patients.

Professor An Gang's team explored
this.

A total of 90 patients
with MM who had undergone ASCT were included in the study.

The results showed that the bone marrow (BM) and SCC MRD negative rates in pre-ASCT patients were 31.
1% and 76.
7%,
respectively.

By comparing the MRD-positive status of different sensitivities and numerical levels of tumor cells, it was found that the proportion of MRD-positive patients in SCC was much lower than that of MRD-positive patients in BM (P<0.
001),
regardless of sensitivity.

At median follow-up of 26.
8 months, negative PRE-ASCT BM MRD was associated with longer PFS (defined here as time from ASCT to disease progression) (55.
88 months vs 34.
17 months, P=0.
0094), but not
with OS (defined here as the time from ASCT to death) (NR vs 58.
86 months, P=0.
11).

And PFS (MRD negative vs positive: 40.
54 months vs.
76.
45 months, P=0.
937) and OS (NR vs.
58.
86 months, P=0.
884) between SCC MRD-positive and SCC MRD-negative patients were similar
.

Compared with both BM and SCC MRD-positive and BM MRD-positive + SCC MRD-negative patients, both BM and SCC had longer
mPFS.

In addition, in patients with optimal remission to cr, MRD-negative patients who achieved CR had a longer
survival compared to MRD-positive patients who achieved CR or VGPR.

The above results show that the MRD status of the pre-ASCT SCC is almost independent of the prognosis of MM, and ASCT
can be performed in TEMM patients who achieve PR.

MrD-negative prognostic value after ASCT is higher
than other prognostic factors in MM patients.

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