Real-world effectiveness and safety of ixazomib-lenalidomide-dexamethasone in relapsed/refractory multiple myeloma

Terpos, Evangelos; Ramasamy, Karthik; Maouche, Nadjoua; Minařík, Jiří; Ntanasis‐Stathopoulos, Ioannis; Katodritou, Eirini; Jenner, Matthew; Plonková, Hana; Gavriatopoulou, Maria; Vallance, Grant; Pika, Tomáš; Kotsopoulou, Maria; Kothari, Jaimal; Jelı́nek, Tomáš; Kastritis, Efstathios; Aitchison, R; Dimopoulos, Meletios Α.; Zomas, Athanasios

doi:10.1007/s00277-020-03981-z

Cited by 34 publications

(43 citation statements)

References 35 publications

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“…At data cutoff, the median follow-up time for all patients included was 10.3 months (range, 1.1-22.9). During the follow-up period, the median cycles of ixazomib therapy received by all patients and those who had ixazomib maintenance were 6 (range, 1-20) cycles and 14 (range, [11][12][13][14][15][16][17][18][19][20], respectively. At data cutoff, 56.5% (48/85) of patients remained on ixazomib treatment, including 90% (9/10) of those receiving single-agent ixazomib as maintenance.…”

Section: Treatment Regimen and Exposurementioning

confidence: 99%

“…Ixazomib is the first oral proteasome inhibitor approved for the treatment in MM patients who have received at least one prior therapy in over 60 countries. The all-oral combination of weekly ixazomib plus lenalidomide and dexamethasone (IRd) has demonstrated durable efficacy and well-tolerated toxicities in phase 3 trial TOURMALINE-MM1 [9,10] and in real-life practice [11].…”

Section: Introductionmentioning

confidence: 99%

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Ixazomib-based frontline therapy in patients with newly diagnosed multiple myeloma in real-life practice showed comparable efficacy and safety profile with those reported in clinical trial: a multi-center study

Xia

et al. 2020

Ann Hematol

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The induction therapy containing ixazomib, an oral proteasome inhibitor, has shown favorable efficacy and safety in clinical trials, but its experience in real-life remains limited. In routine practice, few patients received ixazomib-based induction therapy due to reasons including (1) patients’ preference on oral regimens, (2) concerns on adverse events (AEs) of other intravenous/subcutaneous regimens, (3) requirements for less center visits, and (4) fears of COVID-19 and other infectious disease exposures. With the aim of assessing the real-life effectiveness and safety of ixazomib-based induction therapy, we performed this multi-center, observational study on 85 newly diagnosed multiple myeloma (NDMM) patients from 14 medical centers. Ixazomib-based regimens included ixazomib-lenalidomide-dexamethasone (IRd) in 44.7% of patients, ixazomib-dexamethasone (Id) in 29.4%, and Id plus another agent (doxorubicin, cyclophosphamide, thalidomide, or daratumumab) in 25.9%. Different ixazomib-based therapies were applied due to (1) financial burdens or limitations on local health insurance coverage, (2) concerns on treatment tolerance, and (3) drug accessibility issue. Ten patients received ixazomib maintenance. The median age was 67 years; 43.5% had ISS stage III disease; 48.2% had an Eastern Cooperative Oncology Group performance score ≥ 2; and 17.6% with high-risk cytogenetic abnormalities. Overall response rate for all 85 patients was 95.3%, including 65.9% very good partial response or better and 29.5% complete responses. The median time to response was 30 days. The response rate was similar across different ixazomib-based regimens. Median progression-free survival was not reached. Severe AEs (≥ grade 3) were reported in 29.4% of patients. No grade 3/4 peripheral neuropathy (PN) occurred. Patients received a median of 6 (range 1–20) cycles of ixazomib treatment; 56.6% remained on treatment at data cutoff; 15.3% discontinued treatment due to intolerable AEs. These results support that the ixazomib-based frontline therapy was highly effective with acceptable toxicity in routine practice and the ixazomib oral regimens could be good alternative options for NDMM patients.

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Section: Treatment Regimen and Exposurementioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Ixazomib-based frontline therapy in patients with newly diagnosed multiple myeloma in real-life practice showed comparable efficacy and safety profile with those reported in clinical trial: a multi-center study

Xia

et al. 2020

Ann Hematol

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“…Reported studies on real‐world outcome of IRd are listed in Table 4 14‐18 . Their median age was 65‐75 years, which was higher than that in the TOURMALINE‐MM1 study, and the median age in this study was not much different from their real‐world study.…”

Section: Discussionmentioning

confidence: 69%

“…We counted all treatments, including high‐dose dexamethasone and planned ASCT, as one regimen, so the number of prior therapies might be higher than those of previously reported. Moreover, Terpos et al 18 reported no significant difference in the outcomes between second‐ and third‐line use of IRd therapy. Cohen et al 20 also showed that prior lines of therapy did not affect PFS on IXA combined therapies.…”

Section: Discussionmentioning

confidence: 99%

“…In phase III studies, 10,13 patients were not eligible if they had refractory to PI‐based therapy. In real‐world setting, Terpos et al 18 and Cohen et al 20 showed that prior exposure to PIs was not associated with response to IRd therapy or IXA combined therapies; however, Lawson et al 16 showed that patients who were refractory to PIs showed the shorter time to next treatment. Instead, lenalidomide sensitivity did not affect OS, which might be overcome by other drugs, such as daratumumab, pomalidomide, and carfilzomib.…”

Section: Discussionmentioning

confidence: 99%

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Outcomes of ixazomib/lenalidomide/dexamethasone for multiple myeloma: A multicenter retrospective analysis

Takakuwa

Yamamura

Ohta³

et al. 2021

European J of Haematology

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Objectives This study aimed to investigate real‐world data of ixazomib plus lenalidomide and dexamethasone (IRd) therapy for patients with relapsed and refractory multiple myeloma (RRMM). Methods We retrospectively analyzed 122 patients treated with IRd at 16 centers from May 2017 to January 2019 by using the Kansai Myeloma Forum database. Result At the start of IRd, the median age was 72 years, 66.7% of patients had IgG type, and the median number of prior therapies was 4, comprising bortezomib (85.4%) and lenalidomide (89.3%)‐based regimens. Disease progression and adverse events accounted for treatment discontinuation in 46 and 32 patients, respectively. The median overall survival (OS) was not reached, and the median progression‐free survival (PFS) was 11.9 months. Sensitivity to bortezomib did not affect the PFS, whereas lenalidomide‐refractory patients had significantly lower PFS than lenalidomide‐sensitive patients, who were comparable to TOURMALINE‐MM1 study. The patients with IgG type had significantly better PFS and OS than those with non‐IgG type. Conclusion This study presents the largest real‐world data of patients treated with IRd in Asia. However, in real clinical practice, the patient background is different from the TOURMALINE‐MM1 study, and IRd showed poor efficacy, especially in the non‐IgG type and lenalidomide‐refractory patients with RRMM.

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Efficacy and safety of daratumumab with ixazomib and dexamethasone in lenalidomide‐exposed patients after one prior line of therapy: Final results of the phase 2 study DARIA

Terpos,

Ntanasis‐Stathopoulos,

Gavriatopoulou

et al. 2024

American J Hematol

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The use of lenalidomide in frontline therapy for patients with newly diagnosed multiple myeloma (MM) has increased the number of those who become refractory to lenalidomide at second line. In this context, we assessed the efficacy of daratumumab in combination with ixazomib and dexamethasone (Dara‐Ixa‐dex) in the prospective phase 2 study DARIA. Eligible patients had relapsed/refractory MM (RRMM) after one prior line with a lenalidomide‐based regimen. The primary endpoint was overall response rate (ORR). Secondary endpoints included survival outcomes, safety and changes in biomarkers of bone metabolism. Overall, 50 patients were enrolled (median age 69 years, 56% males). 32 (64%) patients were refractory to lenalidomide, and 17 (34%) had undergone autologous transplant. The ORR was 64% (n = 32); whereas 17 (34%) had a very good partial response or better. The median time to first response was 1.0 month. After a median follow‐up of 23.4 months, the median PFS and OS were 8.1 and 39.2 months, respectively. Furthermore, significant changes in markers of bone metabolism became evident as early as at 6 months on treatment. Regarding safety, 21 (42%) patients had ≥1 grade 3/4 adverse event (AE); the most common was thrombocytopenia (n = 9, 18%). 14 (28%) patients had ≥1 serious AE (SAE), the most common being acute kidney injury and pneumonia (n = 2, each). Four patients died due to infections. In conclusion, second‐line treatment with Dara‐Ixa‐dex in patients with RRMM pre‐treated with a lenalidomide‐based regimen resulted in rapid responses along with a favorable effect on bone metabolism.

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Real-world effectiveness and safety of ixazomib-lenalidomide-dexamethasone in relapsed/refractory multiple myeloma

Cited by 34 publications

References 35 publications

Ixazomib-based frontline therapy in patients with newly diagnosed multiple myeloma in real-life practice showed comparable efficacy and safety profile with those reported in clinical trial: a multi-center study

Ixazomib-based frontline therapy in patients with newly diagnosed multiple myeloma in real-life practice showed comparable efficacy and safety profile with those reported in clinical trial: a multi-center study

Outcomes of ixazomib/lenalidomide/dexamethasone for multiple myeloma: A multicenter retrospective analysis

Efficacy and safety of daratumumab with ixazomib and dexamethasone in lenalidomide‐exposed patients after one prior line of therapy: Final results of the phase 2 study DARIA

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