Deeply understand the continuous treatment of multiple myeloma, the most important points are here | MM continuous treatment series

Introduction "Continuous treatment of multiple myeloma" is the first article in the series, full of dry goods.

The full text is about 1800 words, and it takes about 5 minutes to read.

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

One-minute quick overview of the main points The goal of myeloma treatment is to control the "Darwinian model" of multiple myeloma.
Continuous treatment includes maintenance therapies, as well as different types of continuous therapies, and the methods and dosages of drugs/plans used.
Different full oral treatment programs can better meet the requirements of continuous treatment drugs/programs.
Break the "Darwinian model" of multiple myeloma.
In the past, multiple myeloma (MM) treatments used anti-tumor drugs to reduce tumor burden, but this was far from enough.
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With the deepening of disease recognition and the use of new drugs, researchers describe the goal of myeloma treatment as: controlling the "Darwinian nature" of multiple myeloma [1].

 The so-called Darwinian model refers to the evolving subclones of myeloma becoming more and more independent of the bone marrow environment, and the resistance to anti-myeloma treatments is getting stronger and stronger [1].

How to control this "evolution" mode of tumors? After extensive exploration by researchers, continuous treatment is believed to not only control disease symptoms and deepen treatment response, but also continue to reduce tumor burden and inhibit clonal evolution, thereby obtaining and maintaining minimal residual disease negative (MRDneg) for as long as possible.

That is, MM can be transformed into a chronic or "functionally cured" disease, and long-term molecular remission can be achieved [1,2].

 In the current clinical research, continuous treatment can be said to be a category, which includes a variety of different treatment methods, such as maintenance therapies and different types of continuous therapies.

 In this issue of "Blood Chat Room", let's talk about the ways of continuous treatment? What are the similarities and differences? How to define continuous treatment Different treatment methods Continuous treatment generally refers to the mode of prolonging the treatment time compared to traditional fixed cycle treatment; usually, it refers to the continuous administration of the same induction program (or part of the induction therapy drug) [3].

The main characteristics of an ideal continuous treatment drug or program are: effective, low toxicity, easy to take, and even affordable [1,2].

Continuous treatment is conceptually divided into "maintenance treatment" and "continuous treatment".

In MM patients who are suitable for transplantation (TE), continuous treatment refers to the treatment that occurs after stem cell transplantation, which is also called maintenance treatment.

If TE patients need to be treated with high-intensity consolidation therapy after transplantation, they should receive consolidation therapy first and then maintenance therapy.

In patients who are not suitable for transplantation (TNE), after first-line induction therapy, it is also called maintenance therapy.

In patients who are not suitable for transplantation (TNE), there are two types of continuous treatment.

One is in line with the true meaning of "continuous", that is, continuing treatment until progress or intolerance; the other is less strict "continuing", that is, continuing treatment but the time is still limited.

These two can be called continuous treatment [1].

What is the difference between the drugs/programs of the various continuous treatment methods? "Maintenance treatment" often refers to single-drug or dual-dose therapy given after more intense therapy (autologous stem cell transplantation or dual, triple or even quadruple induction therapy) [2], yes Long-term low-intensity treatment [3].

"Continuous treatment" usually refers to the dual or triple regimen treatment until the disease progresses [2].

Table 1 The characteristics of continuous treatment and maintenance treatment in continuous treatment.
Continuous treatment and maintenance treatment • Usually apply a regimen until the disease progresses • Typical regimen is dual or triple therapy • Is it after ASCT or in dual, triple or even After quadruple remission induction therapy, give a follow-up, long-term, reduced-intensity treatment • The treatment plan is different from the previous high-intensity treatment plan • The typical plan is a single-drug or dual-drug ASCT: autologous stem cell transplantation each lasts What are the commonalities of the drugs used in the treatment? For continuous treatment drugs/programs, the conditions that need to be met are: they must be tolerable for a long period of time, have no cumulative or chronic toxicity, have no adverse effect on the patient’s quality of life, and do not affect the feasibility of subsequent treatment in the event of relapse or Effective and easy to use.

See Table 2 [2] for details.

Table 2 Key requirements for continuous treatment.
Specific content Curative effect/effectiveness•Medications/programs must be effective•Effective for some patient subgroups (including patients with high-risk diseases); for them, continuous treatment is a special need to achieve continuous disease control• It is feasible and effective in real-world practice, and does not affect the feasibility or efficacy of follow-up treatment in the event of recurrence.
In view of the heterogeneity of MM, continuous treatment strategies may need to include multiple drugs with different mechanisms of action to extend specific patient subgroups Disease control time tolerance/safety•Must be tolerable for a long period of time, with almost no cumulative or chronic toxicity, and no serious impact on the patient’s quality of life.
Minimal treatment burden•Through convenient administration method to make treatment burden Minimization is important.

Emphasizes the priority to choose a full oral treatment plan to avoid the burden of patients and caregivers in parenteral administration • Studies have reported that in the treatment of relapsed/refractory diseases, compared to injection-based proteasome inhibitors , Patients prefer the full oral regimen • In the first-line treatment, compared with the injection dosing regimen, the full oral treatment regimen shows a lower economic burden, less activity disturbance, lower productivity loss and greater convenience .

Pay attention to benefits and follow the trend of continuous treatment.
Acceptance of continuous treatment is a prerequisite for this treatment, including the patient's age, social conditions, and the aggressiveness of the disease.

Young patients who usually suffer from aggressive diseases and have good social relationships are more able to withstand continuous treatment, and the acceptance of elderly patients is limited (Figure 1) [1].

Figure 1 The characteristics of the patient and the disease, the willingness of the patient to receive long-term treatment, and the expected results.

High risk: t(4;14), t(14;16), t(14;20), del 17p, non-superdiploid and 1q21 amplification.

Yes+ means gain, and +++ means greater gain.

Regardless of patient acceptance, according to recent studies, the evidence for continued treatment to benefit patients’ survival has become clearer.
It is necessary for clinicians to understand and learn from this treatment trend and philosophy.

Of course, such as the optimal time for continuous treatment, dosage, MRD assessment, and how to make an individualized plan according to the patient's condition, etc.
, will also be further problems to be solved [2]. To be continued.
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In addition to clarifying the concept and characteristics of continuous treatment, "the evidence that continuous treatment is better than fixed cycle treatment", "which drugs are suitable for continuous treatment" and other exciting content will also be in the "continuous treatment of multiple myeloma" "A series of articles will be published one after another, so stay tuned! 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] Musto P, Montefusco V .
Are maintenance and continuous therapies indicated for every patient with multiple myeloma?[J].
Expert Rev Hematol.
2016 Aug;9(8):743-51.
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