How to manage multiple myeloma for a long time?

Introduction "Continuous treatment of multiple myeloma" The second article in the series, fixed cycle treatment or continuous treatment, which is more conducive to the long-term management of multiple myeloma? The full text is about 1,777 words, and it takes about 6 minutes to read.

"One-minute quick overview" helps you quickly understand key information.

One-minute quick overview of the main points In the "patients who are not suitable for transplantation", continuous therapy from treatment to progress or intolerance is in line with the true meaning of "continuous therapy.
"
For patients who are not suitable for transplantation with newly diagnosed MM, first-line Rd Continuous treatment has PFS benefit compared with fixed cycle treatment.

Continuous treatment after recurrence of MM patients has clinical benefits, and IRd and other programs can improve survival prognosis.

In the series of articles on continuous treatment of myeloma, "A deep understanding of continuous treatment of MM, the most important points are in As mentioned here, continuous treatment of myeloma includes a variety of treatment methods.

Among them, “in patients who are not suitable for transplantation (TNE), treatment until disease progression (PD) or toxic intolerable continuous therapy (continuous therapy)” is in line with “ The true meaning of "continuous" treatment [1].
In
this issue of "Blood Chat Room", we will talk about "the advantages and research evidence of MM first-line and continuous treatment after recurrence".
Is the
first-line continuous treatment of TNE patients better than fixed cycle treatment Compared with Rd or MPT fixed cycle therapy, continuous Rd treatment has PFS benefit.
Phase 3 FIRST trial evaluated lenalidomide-low-dose dexamethasone in TNE newly diagnosed multiple myeloma (NDMM) patients ( Rd) continuous treatment, Rd fixed cycle treatment and standard regimen of melphalan-prednisone-thalidomide (MPT) fixed cycle treatment [2,3,4].

The trial included 1623 patients who were randomly assigned to the Rd continuous treatment group (Rd 28-day regimen treatment until PD; 535 cases) or Rd 18 cycle group (Rd 28-day regimen treatment for 18 treatment cycles, 72 weeks in total; 541 cases) or MPT Group (MPT 42-day regimen for 12 treatment cycles, 72 weeks in total; 547 cases).

The primary endpoint was to compare the progression-free survival (PFS) between the Rd continuous treatment group and the MPT group [3].

01 Preliminary analysis showed that the median PFS (25.
5 months) of patients in the Rd continuous treatment group was significantly better than that of the Rd 18 cycle group (20.
7 months) and the MPT group (21.
2 months); the risk of progression or death in the Rd continuous treatment group Compared with the MPT group, it was reduced by 28% (HR 0.
72; P＜0.
001), and compared with the Rd 18 cycle group by 30% (HR 0.
7; P＜0.
001); Rd continuous treatment group (75%) and Rd 18 cycle group (73%) The remission rate was significantly higher than that of the MPT group (62%); the 4-year overall survival (OS) rate of the Rd continuous treatment group was significantly higher than that of the MPT group (59% vs 51%) [2, 3].

02 A median follow-up of 67 months, the test data further confirmed the above results: the median PFS of the Rd continuous treatment group was significantly longer than that of the MPT group (HR 0.
69) and the Rd 18 cycle group (HR 0.
70); the Rd continuous treatment group ( 32.
6%) the 4-year PFS rate more than doubled compared with the Rd 18 cycle group (14.
3%) and the MPT group (13.
6%); the median OS of the Rd continuous treatment group was longer than that of the MPT group by 10 months, which was the same as Rd 18 cycle The group is similar (Figure 1); the incidence of discontinuation due to disease progression in the Rd continuous treatment group (51%) is lower than that of the Rd 18 cycle group (67%) and the MPT group (62%) [2,4,5]; Rd Continuous treatment did not affect the patient’s quality of life [2]; Figure 1 FIRST trial OS final analysis results This study fully illustrates that compared with fixed cycle treatment, continuous treatment until progression or intolerance significantly improves the survival of MM beneficial.

What does the study of continuous treatment after MM recurrence show? In addition to applying continuous treatment to newly diagnosed MM patients, researchers have also explored the effects of new drugs for continuous treatment after MM relapse/refractory [5].

Continuous treatment with immunomodulatory drugs has clinical benefits.
1.
In the MM-009 study, RRMM patients were randomly assigned to receive lenalidomide + dexamethasone (RD) or placebo + dexamethasone until PD.

The median follow-up was 17.
6 months.
The median time to disease progression (TTP; 11.
1 months vs 4.
7 months; P<0.
001) and median OS (29.
6 months vs 20.
2 months; P<0.
001) in the RD group were more comforting The drug + dexamethasone group was significantly prolonged, and the proportion of patients with ≥ partial remission (PR) was significantly higher (61.
0% vs 19.
9%; P<0.
001).

2.
The MM-010 study is similar to MM-009, in that RRMM patients receive RD or placebo + dexamethasone treatment until PD.
The difference is that the location of the study is different.

The median follow-up was 16.
4 months.
The median TTP (11.
3 months vs 4.
7 months; P<0.
001) and median OS (not reaching vs 20.
6 months; P=0.
03) in the RD group were compared with those in the placebo+dexamethasone group Significantly prolonged, and significantly more patients had ≥PR (60.
2% vs 24.
0%; P<0.
001).

3.
The pooled analysis of the MM-009 and MM-010 studies confirmed the significant efficacy and survival benefits of continuous lenalidomide treatment for RRMM patients.

The analysis showed that the median TTP (13.
4 months vs 4.
6 months; P<0.
001), median PFS (11.
1 months vs 4.
6 months; P<.
001) and median OS (38.
0 months vs.
31.
6 months; P=0.
045) Compared with the placebo+dexamethasone group, it was significantly prolonged, and the overall response rate (60.
6% vs 21.
9%; P<0.
001) was significantly improved [5].

4.
In the MM-003 trial, RRMM patients were randomly assigned to receive pomalidomide + low-dose dexamethasone or high-dose dexamethasone alone until PD.

After a median follow-up of 10.
0 months, compared with the high-dose dexamethasone group, the median PFS (4.
0 months vs 1.
9 months; P<0.
0001) and median OS in the pomalidomide + low-dose dexamethasone group (12.
7 months vs 8.
1 months; P=0.
0285) Significantly longer.

Continuous treatment with the oral proteasome inhibitor ixazomib has significant benefits! In addition to immunomodulatory drugs, there are also many studies that use new drugs such as proteasome inhibitors (PIs) and antibody drugs as continuous treatment after relapsed/refractory MM.

Let us take an example of oral PIs characterized by clinical efficacy, safety, and convenience.

The TOURMALINE-MM1 trial compared the oral proteasome inhibitor ixazomib combined with Rd (IRd) and placebo-Rd continuous treatment for RRMM patients, that is, the two groups of patients were treated until the disease progressed or was intolerable.

With a median follow-up of 14.
7 months, the median PFS of the IRd group was significantly longer than that of the placebo-Rd group (20.
6 months vs 14.
7 months; P=0.
01) [6].

The TOURMALINE-MM1 extended study in China showed that after a median follow-up of 7.
4 months and 6.
9 months in the IRd group and placebo-Rd group, respectively, the median PFS of the IRd group was significantly improved compared with the placebo-Rd group (6.
7 months vs 4.
0 Month; P=0.
035).

After a median follow-up of 20.
2 months and 19.
1 months in the IRd group and the placebo-Rd group, respectively, the median OS of the IRd group was significantly longer than that of the placebo-Rd group (25.
8 months vs 15.
8 months; P=0.
001) [7 ].

To be continued.
.
.
There are still many topics about continuous treatment.
Next, "Which drugs are suitable for continuous treatment of MM" and other exciting content will be provided in the "Continuous Treatment of Multiple Myeloma" series of articles, please stay tuned! The little research that everyone is doing, come and move your little finger! ↓↓↓References[1]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.
[2]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.
[3]Benboubker L , Dimopoulos MA, Dispenzieri A, et al.
Lenalidomide and dexamethasone in transplant-ineligible patients with myeloma[J].
N Engl J Med.
2014 Sep 4;371(10):906-17.
[4]Facon T, Dimopoulos MA , Dispenzieri A, et al.
Final analysis of survival outcomes in the phase 3 FIRST trial of up-front treatment for multiple myeloma[J].
Blood.
2018 Jan 18;131(3):301-310.
[5]Richardson PG ,