key: cord-332788-8lq9qygn
authors: Manda, Sudhir; Yimer, Habte A.; Noga, Stephen J.; Girnius, Saulius; Yasenchak, Christopher A.; Charu, Veena; Lyons, Roger; Aiello, Jack; Bogard, Kimberly; Ferrari, Renda H.; Cherepanov, Dasha; Demers, Brittany; Lu, Vickie; Whidden, Presley; Kambhampati, Suman; Birhiray, Ruemu E.; Jhangiani, Haresh S.; Boccia, Ralph; Rifkin, Robert M.
title: Feasibility of Long-Term Proteasome Inhibition in Multiple Myeloma by In-Class Transition from Bortezomib to Ixazomib
date: 2020-07-06
journal: Clin Lymphoma Myeloma Leuk
DOI: 10.1016/j.clml.2020.06.024
sha: 
doc_id: 332788
cord_uid: 8lq9qygn

BACKGROUND: The ongoing US MM-6 study is investigating in-class transition (iCT) from parenteral bortezomib-based induction to all-oral ixazomib-lenalidomide-dexamethasone (ixazomib-Rd) with the aim of increasing proteasome inhibitor (PI)-based treatment adherence/duration while maintaining quality of life (QoL) and improving outcomes. PATIENTS AND METHODS: US community sites are enrolling non-transplant-eligible newly diagnosed multiple myeloma (MM) patients with no evidence of progressive disease after 3 cycles of bortezomib-based therapy to receive ixazomib-Rd (up to 39 cycles or until progression/toxicity). Patients use mobile/wearable digital devices to collect actigraphy (activity/sleep) data and electronically complete QoL/treatment satisfaction/medication adherence questionnaires. Primary endpoint: progression-free survival (PFS); key secondary endpoints include response rates and therapy duration. RESULTS: At data cutoff, 84 patients had been treated (median age 73 years; 44% ≥ 75 years; 49% male; 15% black/African American; 10% Hispanic/Latino); 62% of patients remain on therapy. Mean duration of total PI therapy was 10.1 months and of ixazomib-Rd was 7.3 months. With 8 months median follow-up, 12-month PFS rate was 86% (95% confidence interval, 73–93) from both the start of bortezomib-based treatment and the start of ixazomib-Rd. Overall response rate was 62% (complete response [CR], 4%; very good partial response [VGPR], 25%; partial response [PR], 33%) after bortezomib-based induction and 70% (CR, 26%; VGPR, 29%; PR, 15%) after iCT. The ixazomib-Rd safety profile was consistent with previous clinical trial data. QoL/treatment satisfaction were maintained. CONCLUSION: US MM-6 patients are representative of the real-world US MM population; iCT may permit prolonged PI-based therapy with promising efficacy, without impacting patients’ QoL/treatment satisfaction.

Independent (11) US Oncology Network (8) Veterans Affairs (3) Site type 0 100 After btz-based induction After iCT to ixaozmib-Rd

Proteasome inhibitors (PIs) are a cornerstone of treatment for transplant-eligible and -ineligible patients with newly diagnosed multiple myeloma (NDMM) and for those with previously treated disease. 1 In transplant-ineligible patients, compared with non-PI-based therapy, PI-based therapy has improved both progression-free survival (PFS) and overall survival (OS) in global phase 3 randomized controlled trials. [2] [3] [4] Additionally, data show that longer, continuous PI-based therapy results in prolonged PFS and OS versus shorter, fixed-duration therapy. 5, 6 However, real-world outcomes often do not match those obtained in clinical studies, 7-10 and median treatment duration for PI-based therapy is often shorter in routine clinical practice than in clinical trials. 7, 9, 11 This disparity may be due to various factors including: older age; high comorbidity burden; socioeconomic status; ethnicity/racial differences; poor treatment adherence; burden of repeated intravenous/subcutaneous administration (which can negatively impact health-related quality of life

[HRQoL] 12 ); cost considerations; and toxicity (e.g. peripheral neuropathy [PN] with bortezomib, which can worsen with prolonged exposure, potentially leading to treatment discontinuation 2, 13 ). 7 Additionally, many reasons may make it difficult for patients to travel or access infusion centers in order to receive treatment at a clinic (e.g. environmental conditions, travel restrictions, social/family situations), and some patients may prefer to continue treatment outside of a hospital or clinic setting.

Patients are often excluded from clinical trials due to many of the factors listed above, raising concerns that real-world patients are underrepresented in clinical trials. 7 Analyses have shown that up to 40% of real-world NDMM patients would be ineligible for participation in clinical trials. 8, 14, 15 Given that extended treatment with PI-based therapy results in improved outcomes in clinical trials, 5 we believed it would be valuable to conduct a study to assess the potential benefit of continuous, long-term PI-based treatment in a US community setting. A novel approach to facilitate long-term PIbased treatment in routine clinical practice is to utilize an in-class transition (iCT) from a parenteral (bortezomib) to an oral (ixazomib) PI. Parental bortezomib-based therapy is given as induction during early treatment cycles, when more frequent clinic visits may be required for close disease monitoring, followed by subsequent iCT to all-oral ixazomib-based therapy in later cycles to improve convenience during longer-term, outpatient-based management. The iCT is made possible by the availability of ixazomib, an oral, once-weekly, boron-based, reversible PI, 16 which is approved in combination with lenalidomide-dexamethasone (Rd) for the treatment of patients with MM who have received ≥ 1 prior therapy. 17 The feasibility of long-term ixazomib-Rd treatment in patients with relapsed/refractory MM has been demonstrated by both clinical trial and real-world data. Real-world findings [18] [19] [20] [21] [22] [23] [24] suggest that the effectiveness of extended treatment with ixazomib-Rd appears similar to efficacy reported in clinical trials, 25 and that the combination is well tolerated with low rates of grade 3/4 PN. 19, 20, 25 The US MM-6 study is investigating the novel iCT approach with the aim of increasing PI-based treatment duration and adherence, maintaining HRQoL, and improving outcomes in NDMM patients, with a study design that allows centers to follow their standard-of-care procedures for first-line bortezomib-based induction therapy. This US-based study will provide valuable interventional, prospective, real-world data for this iCT approach, and employs novel data collection methodology to evaluate electronic patient-reported outcomes (ePROs) in an entirely community-based setting, including patients from racial/ethnic minorities. Here we address the feasibility of performing such a trial exclusively in the US community setting, and report preliminary data from the first 84 patients enrolled and treated in the ongoing US MM-6 study. 

The primary endpoint is 2-year PFS (PFS defined as time from first administration of ixazomib-Rd to first documentation of PD or death from any cause 

Planned enrollment is approximately 160 patients. Sample size was determined, assuming a 10% loss-to-follow-up rate, to provide 90% power at an alpha of 0.05 to demonstrate trial success with a 2-year PFS rate of > 57%, based on an assumption of a 2-year PFS rate of 62% for this study and an estimated 2-year PFS rate of 50% derived from historical controls. 2, 28, 29 The treatment phase is expected to last for 78 months comprising a 42-month enrollment period and a 36-month ixazomib-Rd treatment period from the date of last patient enrolled. The safety population comprises all patients who receive ≥ 1 dose of study drug regimen (ixazomib-Rd); all enrolled patients are included in the intent-to-treat population. Further detail regarding specific data analyses is provided in the Supplement. Data analysis was performed by the sponsor, contract research organization, steering committee, and authors. All authors had access to the primary clinical trial data.

As of November 18, 2019, 84 patients had been enrolled at 19 study sites and had received ≥ 1 dose of study drug regimen (ixazomib-Rd). Forty-four percent of patients were aged ≥ 75 years, 15%

were Black or African American, 10% were Hispanic/Latino, 29% had creatinine clearance < 60 mL/min, and 99% had any concurrent medical condition ( Table 1 ). The most common induction regimen at the time of iCT to ixazomib-Rd was bortezomib-Rd (85%); 13% of patients were receiving bortezomib-cyclophosphamide-dexamethasone and 2% were receiving other bortezomib-containing regimens (bortezomib-dexamethasone or bortezomib-lenalidomide; Table 1 ). Bortezomib was administered once-and twice-weekly in 86% (68/79) and 14% (11/79) of patients, respectively. The most common dose of bortezomib received was 1.3 mg/m 2 (82%; 67/82 patients).

Mean duration of PI therapy, from the start of bortezomib-based induction, was 10.1 months (Table 2 ). Mean duration of ixazomib-Rd and ixazomib was 7.3 months and 7.0 months, respectively.

Patients have received up to 23.0 months of treatment with ixazomib-Rd to date. At data cut-off, 52

patients (62%) remained on therapy and 32 (38%) had discontinued treatment. Treatment was discontinued due to PD (n = 5), AEs (n = 4), and 'other' reasons (n = 23); the most common 'other' reason for discontinuation was patient and/or physician decision or withdrawal of consent [n = 15] (other reasons included: sufficient response, n = 3, hospitalization, n = 2, inadequate response, death, no reason, each n = 1).

After median follow-up of 8 months, and with enrollment ongoing, 6 patients had progressed and 2 patients had died. The preliminary 12-month PFS rate (95% confidence interval) was 86% (73-93%) both from the start of bortezomib-based induction and from the start of ixazomib-Rd treatment.

Overall response rate (ORR) after bortezomib-based induction (prior to study start) was 62%, with 4%, 25%, and 33% of patients achieving complete response (CR), very good partial response (VGPR), and partial response (PR), respectively, as their best response. Following iCT to ixazomib-Rd, ORR increased to 70%, with CR and VGPR rates increasing to 26% and 29% respectively ( Figure   1 ).

The safety profile of ixazomib-Rd is summarized in Table 3 ; during treatment to date, any-grade treatment-emergent AEs (TEAEs) were reported for 92% of patients. The most common (> 20%) anygrade TEAEs were diarrhea, PN not elsewhere classified (NEC; high-level term), fatigue, and nausea.

The most common (≥ 5%) grade 3 TEAEs were diarrhea, pneumonia, syncope, and anemia ( patients was pneumonia (5%). There have been 2 on-study deaths due to end-stage renal disease (not treatment-related) and pneumonia (treatment-related) (n = 1 each).

At data cut-off, the EORTC QLQ-C30, EORTC QLQ-MY20, TSQM-9, and monthly medication adherence questionnaires had been completed by 97.3%, 97.6%, 98.7%, and 97.4% of patients who received these instruments, respectively (see Supplement for details).

Patient-reported monthly medication adherence (past 4 weeks) was 'excellent' or 'very good' in 78-92% of patients who reported medication adherence in cycles 1-5 ( Figure 2 ); the most common patient-reported reason for not taking medication was development of side effects (6-19%) . Monthly ePRO medication adherence data have been recorded up to a maximum of 24 cycles to date; beyond cycle 5, the number of evaluable patients was < 30% (data available for between 1 and 22 patients in cycles 6 to 24; n = 1 in cycle 24).

At data cut-off, the maximum number of patients for whom EORTC QLQ-C30, EORTC QLQ-MY20, and TSQM-9 scores were available at ePRO baseline and in any given cycle was 49, 50, and 50, respectively. During ixazomib-Rd treatment (through cycle 8, beyond which the numbers of patients with ePRO data were ≤ 10), changes from ePRO baseline in Global Health Status/QoL and treatment satisfaction were relatively small, indicating both were maintained in those patients for whom data were available ( Figure 3 ). Mean change from ePRO baseline on the EORTC QLQ-MY20

PN item was ≤ 0.4 through cycle 8.

At data cut-off for actigraphy analysis (November 15, 2019), data were available for 71 patients; 9160 compliant days of actigraphy data had been recorded out of a total of 10064 days during which actigraphy data were available. The mean (SD) number of steps/day/patient was 2931 (2234), the mean (SD) number of meters/day/patient was 2062 (1595), and the mean (SD) sleep time was 7.90 (2.60) hours/day/patient.

Analyses by age (< 75 years [n = 47] vs ≥ 75 years [n = 37]) are presented in the Supplement.

Baseline demographics and disease characteristics are shown in Supplemental Table A1 . Mean duration of total PI therapy (from start of bortezomib-based induction) was 10.8 and 9.3 months, and mean duration of ixazomib-Rd was 8.0 and 6.4 months, in the younger and older subgroups respectively (Supplemental Table A2 ). ORR after bortezomib-based induction was 57% (including 2% with CR) in patients aged < 75 years and 68% (5% with CR) in those aged ≥ 75 years. Following iCT to ixazomib-Rd, ORR was 68% (30% with CR) in patients aged < 75 years and 73% (22% with CR) in those aged ≥ 75 years (Supplemental Table A3 ). Grade ≥ 3 TEAEs were reported in 45% and 51% of younger and older patients, respectively (Supplemental Table A4 ). Most commonly occurring (≥ 25% in either subgroup) any-grade TEAEs were diarrhea, PN NEC, fatigue, nausea, and back pain (Supplemental Table A5 ). ePRO and actigraphy data were not analyzed by age due to insufficient patient numbers.

This early snapshot of the prospective, interventional US MM-6 study investigates the feasibility of a novel iCT strategy developed to allow real-world, non-transplant MM patients from US community centers to benefit from long-term PI-based therapy. The population for this study includes patients from the community who may not be eligible for clinical trials because of factors that may impact their ability to respond to and/or tolerate treatment, such as older age, poor performance status, advanced disease stage, prevalent comorbidities, and laboratory abnormalities (which may indicate neutropenia, thrombocytopenia, anemia, hypercalcemia, or poor renal or hepatic function). 8, 14, 15, 30 Renal impairment is a common presenting feature in NDMM, and patients with renal impairment are underrepresented in randomized clinical trials due to exclusion criteria based on creatinine clearance level. 15 With median follow-up of 8 months, and 62% of patients treated to date still on therapy, median duration of total PI therapy (from the start of bortezomib-based induction) was 8.8 months and median duration of ixazomib-Rd was 6.1 months. Notably, some patients have already received > 28 cycles of ixazomib-Rd. Although the discontinuation rate appears high, given that US MM-6 data are not yet mature, these findings are promising. Full understanding of the discontinuation rate will require full enrollment and data maturity.

With the study ongoing, responses continue to evolve, with ORR and CR rates increasing following iCT to all-oral ixazomib-Rd. The ORR of 70% after iCT is comparable to the 74% (per International Uniform Response Criteria) reported for bortezomib plus melphalan and prednisone in the VISTA study 3 Activity is being measured in steps/day and sleep duration in hours/day. The mean number of steps/day/patient reported in US MM-6 is comparable to published data for healthy adults aged > 65 years and for adults living with disability and/or chronic illness that may limit mobility and/or physical endurance. 35 Mean sleep duration reported here is also comparable to that determined previously in healthy adults (with no major medical disorders) aged ≥ 60 years 36 and in patients with MM. 37 With longer follow-up, more mature data will be available for analysis in US MM-6. In future MM studies there is the potential for specific algorithms to be applied to actigraphy data in real time to generate health alerts for particular follow up by the treating physician.

In summary, the US MM-6 study is using a novel iCT approach to facilitate long-term, PI-based treatment for real-world, non-transplant patients with NDMM, and is successfully enrolling a patient population representative of real-world patients. Our findings to date represent a unique, interventional, prospective dataset obtained in the US community setting in mostly elderly patients with comorbidities, and including minority racial and ethnic subgroups. In this context, and with enrollment and follow-up ongoing, we demonstrate that iCT from parenteral bortezomib-based induction to all-oral ixazomib-Rd is feasible, allowing long-term PI-based treatment that is well tolerated with promising efficacy, good medication adherence and no adverse impact on patients'

HRQoL or treatment satisfaction.

In addition to offering a viable treatment option for underrepresented patient populations, the ability to transition from a parenteral to an oral treatment regimen could prevent an interruption in a patient's treatment course. In this way, patients with restricted mobility such as the elderly, or those who may prefer to remain outside of a hospital/clinic setting for treatments, can continue to receive beneficial PI-based treatment. This is especially relevant in the context of the COVID-19 pandemic, as many oncology patients may no longer be able to travel to infusion centers for their treatment.

The effective application of digital technology to record treatment adherence and ePROs can help these patients stay 'on track' with their treatment course despite not being able to regularly meet faceto-face with their physician, and may have implications for future clinical trial designs. Our preliminary analysis supports the continued enrollment to the planned 160 patients and further exploration of the benefit of the iCT approach by US region and patient subgroup, including in racial and ethnic minorities. The full benefit of the iCT in the US MM-6 patient population will become more defined as the data continue to mature.

• In MM clinical trials, longer-term or continuous PI-based therapy results in prolonged PFS and OS versus shorter, fixed-duration therapy; however, outcomes in routine clinical practice often do not match those obtained in clinical studies, and median treatment duration for PIbased therapy is often shorter. Furthermore, up to 40% of real-world NDMM patients may be ineligible for participation in clinical trials due to various factors such as age and comorbidity burden. • The US MM-6 study was therefore designed to evaluate a novel iCT approach in the community-based setting with the aims of increasing PI-based treatment duration and adherence, maintaining HRQoL, and improving outcomes in a representative, real-world, community population of NDMM patients.

• The use of this novel iCT approach from parenteral bortezomib-based to oral ixazomib-based therapy facilitates long-term PI-based treatment that is well tolerated in real-world, nontransplant NDMM patients.

• Preliminary findings indicate that the iCT approach results in promising efficacy and high medication adherence, with no adverse impact on patients' HRQoL or treatment satisfaction.

• This study highlights the feasibility of using mobile and wearable digital devices to collect patient-reported outcomes and actigraphy (activity/sleep) data in the setting of routine clinical practice. Such digital approaches may have implications for future clinical trial designs.

• Use of iCT and digital technology for ePRO collection enables continued PI-based treatment and monitoring in patients with restricted mobility who have difficulty traveling to or accessing infusion centers, as well as in those who may prefer to remain outside of a hospital/clinic setting for their therapy.

The authors would like to thank all patients and their families, as well as all investigators for their valuable contributions to this study. They would like to acknowledge Matthew Cantor and Peter Kelly from Koneksa for actigraphy data collection and analysis. They also acknowledge Jenny Wilkinson of 

This study was funded by Millennium Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company. Representatives of the sponsor, who are included in the authorship list, are responsible for study design, the collection, analysis, and interpretation of data, writing the report, and the decision to submit for publication, as described in the Author contributions statement.

Takeda makes patient-level, de-identified data sets and associated documents available after applicable marketing approvals and commercial availability have been received, an opportunity for the primary publication of the research has been allowed, and other criteria have been met as set forth in Takeda's Data Sharing Policy (see https://www.takedaclinicaltrials.com/ for details). To obtain access, researchers must submit a legitimate academic research proposal for adjudication by an independent review panel, who will review the scientific merit of the research and the requestor's qualifications and conflict of interest that can result in potential bias. Once approved, qualified researchers who sign a data sharing agreement are provided access to these data in a secure research environment. 17 (20) 16 (19) 15 (18) 14 (17) 13 (15) 11 (13) 11 (13)

Bortezomib-Rd Note that patients had to continue receiving ixazomib in order to remain on study; dose interruption of ixazomib lasting > 3 weeks, or an interruption at the principal investigator's discretion, was considered discontinuation from ixazomib treatment and the patient was discontinued from the study, although they could be followed for progression-free and overall survival. In addition, at the discretion of the treating physician, patients could discontinue treatment from lenalidomide and/or dexamethasone while continuing on ixazomib treatment and remain on study. On-study deaths 2 (2) Rd, lenalidomide-dexamethasone; TEAE, treatment-emergent adverse events *Modification or discontinuation of any of the three study drugs (ixazomib, lenalidomide or dexamethasone).

TEAEs were defined as AEs that occurred after administration of the first dose, and through 30 days after the last dose, of the study drug regimen (ixazomib-Rd). TEAEs were considered 'serious' if they resulted in death, were life-threatening, required inpatient hospitalization or prolongation of an existing hospitalization (excluding planned hospital admissions/surgical procedures for pre-existing illness/disease unless the condition deteriorated in an unexpected manner during the study), resulted in persistent or significant disability or incapacity, were a congenital anomaly/birth defect, or were a 'medically important event'. *Cut-offs for inclusion were ≥ 10% of patients at any grade or ≥ 5 patients (6%) with grade 3 in the intent-totreat population. † High-level term.

CI, confidence interval; CR, complete response; iCT, in-class transition; MR, minimal response; NE, not evaluable; ORR, overall response rate; PR, partial response; Rd, lenalidomide-dexamethasone;

VGPR, very good partial response.

*ORR includes CR + VGPR + PR. † CR category includes patients who achieved CR/sCR/immunophenotypic CR/molecular CR. weeks, please rate your ability to take your oral cancer medication as prescribed'. Beyond cycle 5, the number of evaluable patients was < 30%. Maximum number of cycles received to date = 25 (n = 1).

Patient-reported monthly medication adherence (past 4 weeks) available up to cycle 24 (n = 1). † Percentages were calculated based on the number of patients who reported medication adherence in each cycle. 

NCCN Guidelines Insights: Multiple Myeloma, Version 1.2020

Bortezomib with lenalidomide and dexamethasone versus lenalidomide and dexamethasone alone in patients with newly diagnosed myeloma without intent for immediate autologous stem-cell transplant (SWOG S0777): a randomised, open-label, phase 3 trial

Bortezomib plus melphalan and prednisone for initial treatment of multiple myeloma

Persistent overall survival benefit and no increased risk of second malignancies with bortezomib-melphalan-prednisone versus melphalan-prednisone in patients with previously untreated multiple myeloma

Effect of cumulative bortezomib dose on survival in multiple myeloma patients receiving bortezomib-melphalan-prednisone in the phase III VISTA study

Bortezomib-containing regimens (BCR) for the treatment of non-transplant eligible multiple myeloma

Interpreting clinical trial data in multiple 13. VELCADE® (bortezomib) for injection. Velcade US Prescribing

The real-world characteristics and outcomes of newly diagnosed myeloma patients ineligible for clinical trials

Patients (Pts) Remain Under-Represented in Clinical Trials Based on Standard Laboratory Parameters and Baseline Characteristics: Analysis of over 3,000 Pts from the Insight MM Global, Prospective, Observational Study

Clinical Pharmacology of Ixazomib: The First Oral Proteasome Inhibitor

NINLARO US Prescribing Information2016

Patients (Pts) -Effectiveness in Routine Clinical Practice Is Similar to the Efficacy in the Phase 3 Tourmaline-MM1 Trial: A Pooled Analysis from the Insight MM Observational Study and the Czech Registry of Monoclonal Gammopathies (RMG)

Closing the Efficacy and Effectiveness Gap: Outcomes in Multiple Myeloma: A Combined Study from the Greek, Czech and UK Databases

*ePRO baseline was defined as the reported measurement at the end of cycle 1 of ixazomib-Rd

Change from ePRO baseline was only calculated at post-ePRO baseline ixazomib-Rd cycles where a value was present, and among patients with an ePRO baseline value. †Data available up to 24 cycles for each measure

This scale has a range of 0-100. Positive and negative changes indicate an improvement and deterioration, respectively, in QoL. EORTC QLQ-MY20 item 43 ('Did you have tingling hands or feet?') measures the burden of peripheral neuropathy symptoms according to the following scores: 1 = Not at all, 2 = A little, 3 = Quite a bit, 4 = Very much

effectiveness', 'convenience' and 'global satisfaction') have a range of 0-100. Positive and negative changes indicate an increase and decrease, respectively, in treatment satisfaction

• In MM clinical trials, longer-term or continuous PI-based therapy results in prolonged PFS and OS versus shorter, fixed-duration therapy; however, outcomes in routine clinical practice often do not match those obtained in clinical studies, and median treatment duration for PIbased therapy is often shorter. Furthermore, up to 40% of real-world NDMM patients may be ineligible for participation in clinical trials due to various factors such as age and comorbidity burden. • The US MM-6 study was therefore designed to evaluate a novel iCT approach in the community-based setting with the aims of increasing PI-based treatment duration and adherence, maintaining HRQoL, and improving outcomes in a representative, real-world, community population of NDMM patients.• The use of this novel iCT approach from parenteral bortezomib-based to oral ixazomib-based therapy facilitates long-term PI-based treatment that is well tolerated in real-world, nontransplant NDMM patients.• Preliminary findings indicate that the iCT approach results in promising efficacy and high medication adherence, with no adverse impact on patients' HRQoL or treatment satisfaction.• This study highlights the feasibility of using mobile and wearable digital devices to collect patient-reported outcomes and actigraphy (activity/sleep) data in the setting of routine clinical practice. Such digital approaches may have implications for future clinical trial designs.• Use of iCT and digital technology for ePRO collection enables continued PI-based treatment and monitoring in patients with restricted mobility who have difficulty traveling to or accessing infusion centers, as well as in those who may prefer to remain outside of a hospital/clinic setting for their therapy.

While long-term proteasome inhibitor therapy improves outcomes in multiple myeloma, many patients cannot tolerate long-term treatment or may require/prefer to continue treatment outside the hospital/clinic. US MM-6 evaluates in-class transition from parenteral bortezomib-to oral ixazomibbased therapy in routine clinical practice. Preliminary results indicate feasibility, prolonged duration of therapy, and promising efficacy and treatment adherence/satisfaction.