2021 ASH is very promising. Regarding the continuous treatment of multiple myeloma, the results of the US MM-6 study have been updated!

Introduction As an academic feast that has attracted much attention in the field of hematology, the 63rd American Society of Hematology (ASH) Annual Meeting will be held in Atlanta, USA on December 11-14, 2021 in a combination of online and offline
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The results of the US MM-6 research update were released at this conference, let us take a look
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In recent years, with the increase of research evidence, the long-term continuous treatment model of multiple myeloma (MM) has been widely accepted [1]
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Ideally, continuous treatment can not only control disease symptoms and deepen treatment response, but also continue to reduce tumor burden and inhibit clonal evolution, so as to obtain and maintain minimal residual disease negative for as long as possible, so that MM can become chronic or "functional".
"Cure" (ie, long-term molecular remission) of diseases [2,3]
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Data show that long-term continuous treatment based on proteasome inhibitors (PIs) can improve the prognosis of MM
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However, in clinical practice, the use of injectable PI for long-term treatment has problems with the patient's body, as well as geographical and/or socio-economic aspects [4]
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So, how can we increase the duration of PIs treatment while maintaining the quality of life of patients and improving their prognosis? Let's take a look at the updated results of the US (US) MM-6 study (Abstract No.
2726) [5]
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US MM-6 study: To explore the feasibility of long-term continuous treatment of PIs in the real world.
The MM1 study has shown the clinical benefits of the all-oral IRd regimen (Ixazomib-lenalidomide-dexamethasone) for relapsed and refractory adult MM Benefits, as well as the advantages of safety and convenience
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The US MM-6 study is to see the benefits of PIs similar drug conversion (iCT) for patients in real clinics, that is, the conversion from the induction therapy of bortezomib for injection to the full oral IRd regimen of ixazomib[6]
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As a community-based, real-world, open-label, single-arm Phase IV study [6], the US MM-6 study included unsuitable transplantation/transplant delay (≥24 months), after 3 cycles of bortezomib induction therapy Patients with newly diagnosed multiple myeloma (NDMM) who have achieved stable disease or better curative effect receive IRd regimen (Isazomib 4mg, administration on days 1, 8, and 15; Lenalidomide 25mg, days 1-21 Administration; dexamethasone 40mg, administered on days 1, 8, 15, and 22; 28 days is a treatment cycle, treatment for 39 cycles, or until the disease progresses or toxicity is unacceptable [5]
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(Note: Iraq The combined use of sarzomib with lenalidomide and dexamethasone to treat adult patients with multiple myeloma who have received at least one previous treatment is the current indication for ixazomib approved in China)
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The
primary endpoint is 2 Annual progression-free survival (PFS) rate
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Key secondary endpoints include partial response (PR) rate, very good PR (VGPR) rate, complete response (CR) rate, and duration of treatment (DOT)
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The
previous median follow-up was 12 The preliminary results of the month showed that the iCT therapy can obtain promising curative effects, and is well tolerated, high compliance, and has no adverse impact on the patient’s health-related quality of life or treatment satisfaction [6]
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Updated results: 18 months PFS The rate reached 84%, and the median DOT converted to IRd treatment reached 11.
7 months.
The updated results showed that as of June 1, 2020, a total of 101 patients were enrolled and received treatment, and the median age was 73 years (81% of patients Age> 65 years)
.
The
vast majority (97%) of patients have ≥1 comorbidities at the beginning of IRd treatment
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As of May 4, 2021, after an additional follow-up of 11 months, the efficacy of the drug after switching to IRd was significantly improved (Table 1): The overall response rate (ORR) was 65% at the end of the 3 cycles of bortezomib induction ( CR 9%, VGPR 25%, PR 32%) increased to 78% after conversion to IRd [Molecular CR (mCR) 1%, strictly CR (sCR) 3%, CR 32%, VGPR 25%, PR 17%]
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The median follow-up was 18.
5 months, and the 18-month PFS rate was 84%
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As of the latest data cutoff, 33 patients (33%) were still receiving treatment; the median DOT for IRd treatment was 11.
7 months, and the median DOT for all PI treatments was 14.
6 months
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Table 1 ORR and CR rates increased with the extension of treatment time after iCT (N=101)* The patient received 3 cycles of bortezomib regimen before entering the study
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The average duration of bortezomib induction therapy is 3 months; due to the real-world nature of the study, the length of the bortezomib treatment cycle varies from protocol to protocol
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✝Molecular complete remission
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‡ Due to rounding, the ORR percentage may not be a summation
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§Data as of June 2020
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¶The data is as of May 2021.
In terms of safety, the safety characteristics of IRd are consistent with the results of previously reported clinical studies
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Premature discontinuation: The main reason is the patient's request, followed by the adverse events during the treatment.
So far, 14 cases (21%) in the study discontinued the drug within 2 cycles of IRd treatment, and 27 cases (40%) were discontinued in 4 cycles The drug was discontinued internally; most of the reported premature discontinuation events were due to patient requests (44%), followed by TEAE (30%; Table 2)
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In addition, the proposed US MM7 iCT study will explore whether the problem of premature drug withdrawal can be reduced through disease education and close patient management among people with relapsed and refractory MM.
It is worth looking forward to
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Table 2 Reasons for premature discontinuation (within 4 cycles of IRd treatment)* The patient received 3 cycles of bortezomib regimen before entering the study
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✝Other reasons for discontinuation include prolonged hospital stay (n=1), doctors determined that the treatment response was good (n=2), doctors determined that the treatment response was not good (n=1), and transfer to hospice care/professional care institutions (n= 1)
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GI: gastrointestinal tract; PD: disease progression Conclusion The US MM-6 study update results show that in the real world, with the extension of follow-up time, the remission rate of NDMM patients receiving iCT therapy increases significantly, and the PFS rate remains high
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It is hoped that the strategy of iCT can help more MM patients benefit from the long-term continuous treatment of PIs and achieve long-term survival! References[1] Shen M, Zhang J, Tang R, et al.
Ixazomib-based maintenance therapy after bortezomib-based induction in patients with multiple myeloma not undergoing transplantation: A real-world study[J].
Cancer Med.
Published online : 2021 Oct 16.
[2] Ludwig H, Zojer N.
Fixed duration vs continuous therapy in multiple myeloma[J].
Hematology Am Soc Hematol Educ Program.
2017 Dec 8;2017(1):212-222.
[3] Dimopoulos MA, Jakubowiak AJ, McCarthy PL,et al.
Developments in continuous therapy and maintenance treatment approaches for patients with newly diagnosed multiple myeloma[J].
Blood Cancer J.
2020 Feb 13;10(2):17.
[4]https: //ashpublications.
org/blood/article/136/Supplement%201/2/472865/In-Class-Transition-iCT-from-Parenteral-Bortezomib[5] https://ash.
confex.
com/ash/2021/ webprogram/Paper150094.
html[6] Manda S, Yimer HA,
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