Mayo Thousand Studies demonstrated that the interval between the end of NDMM induction therapy and transplantation can affect PFS

New advances in multiple myeloma (MM) treatment options and the continued use of autologous stem cell transplantation (ASCT) have significantly improved survival outcomes over the past 20 years, but the role of transplantation has recently been challenged by new drugs and combinations that can effectively control the disease and achieve comparable outcomes
without consolidation transplantation.
This result is primarily driven by the toxicity of transplant-related procedures such as infections, even if its duration has reached a minimum and is usually reversible
.
However, many clinical trials have shown a significant survival benefit with ASCT compared with medical therapy alone, with nearly one-third of patients achieving complete remission (CR) without any additional treatment, and median PFS from diagnosis of 18 months to 2 years
.

Patients who are candidates for first-line transplantation typically receive an induction regimen of 3 to 6 cycles, followed by high-dose melphalan and autologous stem cell
infusions.
Typically, the last induction cycle is completed 3-4 weeks before stem cell mobilization and apheresis; While the use of CXCR antagonists such as Puresaf reduces apheresis delay, other logistical issues can increase the gap
between the end of induction and the initiation of ASCT.
Patients then receive high-dose chemotherapy and a return infuse of stem cells
.

Although many risk factors (e.
g.
, age, obesity, previous radiation exposure) help predict transplant outcomes, it is unclear whether disease exacerbation during the drug-free period between the date of last chemotherapy and the date of stem cell infusion predict high-risk disease and poor
post-transplant clinical outcomes 。 In order to evaluate the effect of chemotherapy-free period on progression-free survival (PFS) and overall survival (OS) after ASCT, Professor Mayo Shaji Kumar et al.
reviewed the data of 1055 NDMM patients who received autologous transplantation in our center over 15 years, and found that the time from the end of induction therapy to the start of transplantation was 33 days, and the PFS of patients > 33 days was significantly worse
.
The detailed results were published today in Bone Marrow Transplantation
, the official journal of the European Society of Blood and Marrow Transplantation (EBMT).

Research methods

This retrospective cohort study included all NDMM patients
who attended the Mayo Clinic from 2004 to 2018 and received first-line ASCT within 1 year of diagnosis.
Patients with disease progression during induction therapy, as well as patients receiving pulse therapy with cyclophosphamide prior to mobilization, were excluded, as it artificially extended the time
to transplantation compared to standard regimens.
In addition, to ensure cohort homogeneity, all patients
receiving maintenance therapy or other chemotherapy regimens after stem cell harvesting were excluded.

The authors first assessed the duration of each patient's induction regimen, recorded the exact date of the patient's last chemotherapy, and divided the patients into 2 groups based on the median-to-transplant time (TTT) calculated from the date of the last chemotherapy to the date of stem cell infusion; The administration of the pretreatment regimen was then also collected and the level
of biochemical remission achieved prior to transplantation was determined according to IMWG criteria.
Baseline clinical features of the entire cohort were collected, Del17p, T (4; 14)、t(14; 16)、t(14; 20) Gain1Q abnormalities are high-risk].

Study endpoints were PFS (from stem cell infusion date to date of biochemical progression or intensive therapy) and OS (from stem cell infusion date to all-cause death date).

Research results

A total of 1055 NDMM patients received autologous stem cell transplantation
within one year of diagnosis.
The median age at diagnosis was 61.
4 years, and 332 patients (35.
7%) had high-risk FISH abnormalities
.
In the entire cohort, 461 (43.
8%) patients were mobilized with G-CSF alone, and 588 (55.
9%) were mobilized with Ploroxafor
.
In terms of pretreatment, 893 (84.
6%) patients received melphalan 200 mg/m2, and the remaining patients [¹¹² (10.
6%)] received a low-dose regimen or other melphalan regimen [50 (4.
7%)].

The median PFS and OS after stem cell infusion date were 33.
4 and 122.
3 months
, respectively.
Baseline clinical features are shown in Table 1
.

The median TTT since the last chemotherapy date was 33 days, so the cohort was grouped
according to the median TTT (33 days).
PFS was found to be significantly longer in patients with a TTT ≤ 33 days than in patients with > 33 days (35.
6 vs.
32.
1 months, p< 0.
03), but no difference in OS (128 vs.
122.
2 months, p= 0.
68) (Figures 1 and 2).

The authors then grouped patients according to interquartile TTT and found that patients with TTT ≤ 27 days (1st quartile) had significantly longer PFS compared with those with TTT > 42nd day (4th quartile) (36.
7 vs.
30.
9 months, p< 0.
01), but the difference in OS remained insignificant (115.
8 vs.
124.
4 months, p=0.
33) (Figures 3 and 4).

Univariate analysis found that HR = 1.
17 (p< 0.
03)
for PFS in patients with TTT > 33 days compared with patients with TTT ≤ 33 days.
The authors then performed a multivariate analysis to determine whether TTT prolongation was an independent risk factor for PFS shortening in patients with MM, and the model took into account age, biochemical response before transplantation, pretreatment dose, and FISH results at diagnosis, and found an increased risk of PFS shortening in patients with TTT prolongation (HR = 1.
19, p< 0.
03).

The authors then divided the patients into interquartiles and compared the 1st quartile to the 4th quartile, resulting in univariate analysis of PFS showing HR = 1.
37 (p< 0.
01) for patients in TTT 4th quartile and HR = 1.
34 (p< 0.
01)
for patients with multivariate analysis.

The authors also performed a subgroup analysis based on biochemical responses obtained prior to transplantation, classifying patients into "good" remitters (≥VGPR) and "poor" remitters (37.
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