Ixazomib-Based Maintenance Therapy Improves Prognosis of Patients with Multiple Myeloma: A Real-World Study
Authors: Hong Xiuli , Chen Jie , Lu Jingyuan , Lu Quanyi 
Published: December 2024

Background

The prognosis of multiple myeloma (MM),has been improved by the emergence of novel agents such as immunomodulatory drugs and proteasome inhibitors, which have become the cornerstone of MM treatment. The persistent nature of MM and the relatively long survival of MM patients have raised concerns over the safety and efficacy of continuous long-term therapy. The all-oral regimen consisting of ixazomib(I), lenalidomide(R), and dexamethasone(D)(IRD) has been widely used in the treatment of myeloma, which greatly improves patient adherence and facilitates medication application; however, there is a lack of real-world clinical data as to whether IRD maintenance therapy improves patient's outcome. This study reports long-term real-world data from 59 myeloma patients who were switched to IRD maintenance therapy.

Methods

The median age of 59 patients with multiple myeloma was 66 years with 35 (59%)patients≥65 years. International Myeloma Working Group (IMWG) risk stratification was highrisk in 45 (76%)patients, and Intermediate risk in 14 (24%)patients. The amplification of 1q21 (1q21 amp) was found in 18 (31%) patients.

Patients included in the observation group had received at least two courses of different induction therapies with treatment outcomes of stable disease(SD) or better were converted to an IRD all-oral regimen with weekly ixazomib 4mg or 3mg for 3 weeks, lenalidomide 25mg qd for 21d consecutively, and weekly dexamethasone 20mg orally for 3 weeks. The patients were evaluated for the remission rate (patients reached partial response[PR], very good partial response[VGPR], and complete response[CR]), duration of remission, and adverse events (AEs) after IRD treatment. The cutoff time was July 1, 2024.

Results

Fifty-nine patients were treated with the IRD regimen for a median of 25 months(12-55), with a maximum duration of 55 months. Twenty-two (37.3%) patients received oral therapy at the cutoff for follow-up. After six courses of treatment, 79.7% of patients reached (15 vs 47)VGPR, with 6 of 9 (66.7%)SD patients achieving VGPR or higher after switching to oral therapy and 15 of 24 (62.5%)PR patients achieving VGPR.

Subgroup analyses showed that patients with 1q21 amp, either in the IMWG high-risk or Intermediate-risk group, could benefit from a treatment switch, with the VGPR rate increasing from 50% to 78% after switching to I-base oral regimens and increasing to 73% and 100% in high-risk and Intermediate-risk patients, respectively.

In patients ≥65 years of age after switching to an oral I-base regimen, VGPR rates increased from 28.5% to 80% with a mean DOT of 8.2 months when evaluated over 6-12 courses.

The ixazomib-based oral maintenance regimen was generally well-tolerated by patients. The major adverse effect of the bortezomib-based induction regimen was peripheral neuropathy (PN), which reached grade 3 or more in 7 patients. No TAEs above grade 3 occurred after switching treatments. The major adverse effect of the ixazomib-based oral maintenance regimen was diarrhea, which mostly disappeared after the intervention, with only one patient seeing a worsening of PN that led to termination of treatment.

Discuss

Clinical studies have shown that continuous maintenance therapy after induction therapy for MM improves treatment outcomes and prognosis, especially to patients at high cytogenetic risk. Real-world data from our center showed that maintenance therapy with IRD improved the depth of remission and reduced the risk of disease progression in high-risk patients. Although the induction therapy regimen before the study was different, 80% of the patients improved the depth of remission after long-term sustained IRD maintenance therapy, which provides an option for follow-up treatment of high-risk myeloma patients.

Despite the limited cases in this study, we still noticed that the IRD regimen achieved significant therapeutic responses in elderly patients with comorbidities, regardless of age, gender, ISS stage, renal insufficiency, comorbidities status, first-line therapeutic exposures, or 1q21+status, which is similar to literature. The main adverse effect of the maintenance regimen was diarrhea. The longest maintenance treatment duration reached 55 months in this study, with no significant hematologic toxicity, PN exacerbation, or herpes zoster infection during treatment. Patient compliance and quality of life were improved.