To improve MM treatment adherence, think in terms of these aspects

Proteasome inhibitors (PIs) have become the cornerstone of MM therapy ^[5].

How can adherence and persistence of PIs-based therapies be improved in routine clinical practice?

The US-MM6 study is a real-world exploration of the clinical efficacy of switching therapy strategies (iCTs) from bortezomib-based induction therapy to an all-oral IRd regimen (ixazomib-lenalidomide-dexamethasone) with the goal of increasing adherence and duration of PI-based therapy, maintaining patients' quality of life, and improving outcomes; The study recruited patients with newly diagnosed MM, who received 3 cycles of bortezomib-based induction therapy, and continued IRd regimen treatment for patients without disease progression (PD); Preliminary results suggest that iCT treatment is feasible, with a long course of treatment, good efficacy, and high treatment adherence and satisfaction ^[5,6].

A Chinese study published in Leukemia Lymphoma this year also explored the safety and efficacy of IRd regimens in real-world MM patients, involving conversion therapy patients consistent with US-MM6 research philosophy ^[6].

The study retrospectively analyzed the clinical data of 24 patients with MM who received at least 2 cycles of IRd regimen treatment at the Union Hospital affiliated to Tongji Medical College of Huazhong University of Science and Technology from January 2019 to January 2021, and observed and analyzed the effect and adverse reactions
of IRd regimen in the treatment of MM.
These patients included 19 treatment-naïve patients (conversion group) and 5 relapsed refractory patients (relapsed refractory group)
who were effective in bortezomib induction but switched to IRd regimen due to adverse effects or other reasons.

In the conversion group, iCT efficacy data showed:

• There were 8 complete responses (CR), 5 very good partial responses (VGPR), 5 partial responses (PR), and 1 PD, with an overall response rate (ORR) of 94.
  7% (18/19), that is, almost all patients responded to the IRd regimen;

  
  

• 57.
  9% (11/19) of patients maintained the original efficacy;

  
  

• 36.
  8% (7/19) of patients had a deeper degree of remission, and the best efficacy of 5 and 2 patients increased from VGPR and PR to CR, respectively.
  

  
  

• There was a statistically significant difference in median PFS time between the relapsed and refractory groups and the conversion group (7-month ratio not achieved, P=0.
  018);

The investigators concluded that because all patients in the switching group had previously used bortezomib and achieved at least PR, it was indicated that the IRd regimen could further deepen the remission on the basis of the effective treatment of bortezomib; In addition, PD after switching to IRd regimen in one patient may be related
to multiple cytogenetic abnormalities [13q14, 17p13 deletion, 1q21 amplification, t(4,14)].

In terms of tolerability and safety, IRd regimens were well tolerated and most adverse effects were manageable
.
Common adverse reactions are hematological adverse reactions, peripheral neuropathy (PN), fatigue, gastrointestinal reactions, infection, and the incidence of grade 3~4 adverse reactions is 25.
0%.

Most patients with pre-existing PN had some relief of pain and numbness, and only one patient without prior PN developed PN during IRd regimen treatment; This further confirms that ixazomib is less neurotoxic than bortezomib and adverse effects are more tolerable and controllable
.