In-Class Transition from Bortezomib-Based Therapy to IRd is an Effective Approach in Newly Diagnosed Multiple Myeloma

Figures & data

Table 1. Patient baseline and disease characteristics after inverse probability of treatment weighting.

Characteristic	IRd cohort (N = 113 ^† )	V-based cohort (N = 102 ^† )	p-value
Median follow-up period, months (range)	20.3 (4.3–41.9)	15.8 (0.3–40.8)	0.0027
Median age, years (range)	75.0 (47.0–90.0)	74.8 (44.3–88.0)	0.1874
Age category, years, n (%)   <55   55–64   65–74   ≥75 years	4 (3.4) 15 (12.9) 28 (24.5) 67 (59.2)	7 (6.4) 17 (17.0) 28 (27.2) 50 (49.3)	0.4419
Male, n (%)	64 (56.7)	52 (51.3)	0.4328
ECOG PS, n (%)   0   1   2	16 (14.2) 55 (48.4) 42 (37.4)	13 (12.8) 59 (58.1) 30 (29.1)	0.3493
LDH, n (%)   Normal (≤240 U/L)   High (>240 U/L)   Missing	61 (54.1) 12 (10.5) 40 (35.4)	42 (40.9) 17 (16.4) 44 (42.7)	0.1273
ISS disease stage (at initial diagnosis), n (%)   I   II   III	19 (17.1) 39 (34.1) 55 (48.8)	21 (20.7) 39 (37.9) 42 (41.4)	0.5404
Induction regimen, n (%)   VRd   VCd   VRCd	90 (79.5) 20 (17.7) 3 (2.8)	79 (77.3) 20 (19.5) 3 (3.1)	0.9309
CCI score, n (%)   0   1   2   3+	36 (31.4) 17 (14.9) 20 (17.6) 41 (36.0)	39 (37.7) 13 (13.0) 21 (20.2) 30 (29.0)	0.6268
Race, n (%)   White   Black   Asian   Other   Missing/Unknown	78 (69.0) 23 (20.6) 2 (1.8) 9 (8.1) 1 (0.5)	73 (71.4) 16 (16.0) 1 (0.6) 4 (4.0) 8 (8.0)	0.0364
Renal impairment ^‡ , n (%)   Yes   No   Missing	25 (21.8) 88 (78.2) 0	20 (19.9) 78 (76.7) 3 (3.4)	0.1400
Facility type, n (%)   Community   Academic	113 (100) 0	93 (91.5) 9 (8.5)	0.0015

† IPTW-weighted cohorts; percentages may not sum to 100% due to rounding.

‡ Defined as estimated glomerular filtration rate <40 ml/min/1.73 m² calculated from creatinine levels using the Modification of Diet in Renal Disease study equation [11,12].

C: Cyclophosphamide; CCI: Charlson Comorbidity Index; d: Dexamethasone; ECOG PS: Eastern Cooperative Oncology Group performance status; I: Ixazomib; IPTW: Inverse probability of treatment weighting; ISS: International Staging System; LDH: Lactate dehydrogenase; R: Lenalidomide; V: Bortezomib.

Reprinted from Poster P947 presented at the 27th Congress of the European Hematology Association (EHA) 2022, Copyright © 2022 The Author(s) [9].

Abstract Book for the 27th Congress of the European Hematology Association. Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the European Hematology Association [10].

Figure 1. Adjusted ORR* in the IRd and V-based inverse probability of treatment weighted cohorts.

*Defined as the proportion of patients with partial response, very good partial response, complete response and stringent complete response during initial treatment regimen and prior to disease progression.

IPTW: Inverse probability of treatment weighting; IRd: Ixazomib-lenalidomide-dexamethasone; ORR: Overall response rate; V: Bortezomib.

Reprinted from Poster P947 presented at the 27th Congress of the European Hematology Association (EHA) 2022, Copyright © 2022 The Author(s) [9].

Abstract Book for the 27th Congress of the European Hematology Association. Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the European Hematology Association [10].

Figure 2. Adjusted DOT regimen* in the IRd and V-based inverse probability of treatment weighted cohorts.

*Time from the index date (date that patients began V-based therapy) to the date of the last administration of any of the three study drugs in the IRd regimen or first-line V-based regimen for comparators (event), death (due to any cause, event), or end of follow-up (censored).

DOT: Duration of treatment; IPTW: Inverse probability of treatment weighting; IRd: Ixazomib-lenalidomide-dexamethasone; V: Bortezomib.

Reprinted from Poster P947 presented at the 27th Congress of the European Hematology Association (EHA) 2022, Copyright © 2022 The Author(s) [9].

Abstract Book for the 27th Congress of the European Hematology Association. Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the European Hematology Association [10].

Table 2. Time-to-event outcomes after inverse probability of treatment weighting.

Characteristic	IRd cohort (N = 113) ^†	V-based cohort (N = 102 ^† )	p-value
Median DOT, months (95% CI)	10.8 (6.5–24.4)	5.3 (4.3–7.0)	<0.0001
DOT, % (95% CI)   At 6 months   At 12 months   At 18 months   At 24 months	66.7 (51.8–78.0) 48.8 (34.8–61.3) 43.2 (29.7–56.0) 37.0 (23.7–50.4)	42.6 (31.0–53.7) 15.1 (8.1–24.3) 3.2 (0.9–7.9) 0.7 (0.1–4.2)
Median PFS, months (95% CI)	NR (36.2–NR)	NR (NR-NR)	0.7235
PFS, % (95% CI)   At 6 months   At 12 months   At 18 months   At 24 months	96.0 (81.2–99.2) 86.9 (69.6–94.7) 85.7 (68.1–94.0) 85.7 (68.1–94.0)	95.3 (87.1–98.4) 87.5 (76.9–93.5) 80.1 (67.8–88.1) 76.5 (62.6–85.8)
Median OS, months (95% CI)	NR (39.5–NR)	NR (32.1–NR)	0.3341
OS, % (95% CI)   At 6 months   At 12 months   At 18 months   At 24 months	100 (100–100) 99.3 (61.0–100) 96.9 (80.9–99.5) 94.0 (77.7–98.5)	98.0 (90.5–99.6) 96.6 (88.2–99.1) 90.4 (79.7–95.6) 84.9 (70.6–92.6)

† IPTW-weighted cohorts.

DOT: Duration of treatment; IRd: Ixazomib-lenalidomide-dexamethasone; IPTW: Inverse probability of treatment weighting; NR: Not reached; OS: Overall survival; PFS: Progression-free survival; V: Bortezomib.

Figure 3. Adjusted outcomes in the IRd and V-based inverse probability of treatment weighted cohorts.

(A) Adjusted PFS; (B) Adjusted OS.

*IPTW-weighted cohorts.

IPTW: Inverse probability of treatment weighting; IRd: Ixazomib-lenalidomide-dexamethasone; NE: Not estimable; PFS: Progression-free survival; OS: Overall survival; V: Bortezomib.

Reprinted from Poster P947 presented at the 27th Congress of the European Hematology Association (EHA) 2022, Copyright © 2022 The Author(s) [9].

Abstract Book for the 27th Congress of the European Hematology Association. Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the European Hematology Association [10].

Table 3. Reasons for discontinuation of IRd and V in the V-based inverse probability of treatment weighted cohorts.

	IRd cohort (N = 113)	V in the V-based cohort (N = 102)
Reason for discontinuation, n (%)	72 (63.3)	73 (71.9)
Progressive disease	16 (22.6)	9 (12.8)
Adverse event	13 (17.6)	18 (24.4)
Peripheral neuropathy	–	8 (44.7)
Not specified	5 (36.8)	–
Skin rash	–	3 (15.9)
Worsening peripheral neuropathy	2 (13.3)	–
Diarrhea	1 (11.6)	1 (4.3)
Anorexia/fatigue	1 (11.4)	–
Infections and infestations	–	1 (8.3)
Fatigue	–	1 (8.0)
Other pulmonary: pneumonia	–	1 (7.3)
Lower extremity weakness	1 (5.2)	–
Nausea/diarrhea/vomiting	1 (4.8)	–
Peripheral sensory neuropathy	1 (4.6)	–
Unacceptable toxicity but also complete response	1 (4.6)	–
Constipation	–	1 (4.3)
Other: diffuse skin rash (unknown type)	–	1 (4.2)
Bilateral sensory neuropathy (feet)	1 (3.9)	–
Worsening back pain	1 (3.8)	–
Other: angiodema	–	1 (3.1)
Patient request	34 (48.0)	1 (0.8)
Planned therapy completed	–	33 (44.6)
Inadequate response	1 (0.8)	1 (1.8)
Other	8 (11.9)	11 (15.5)
Patient achieved sufficient response	2 (25.6)	6 (50.6)
Hospitalization/nursing facility/hospice	3 (33.8)	1 (4.9)
Death	1 (7.9)	3 (23.9)
Unknown	1 (13.2)	2 (15.6)
Second primary malignancy	1 (6.6)	–
Discontinued study (but remaining under follow-up)	1 (6.5)	–
Lost to follow-up	–	1 (4.9)

Percentages may not sum to 100% due to rounding.

IRd: Ixazomib-lenalidomide-dexamethasone; V: Bortezomib.

Reprinted from Poster P947 presented at the 27th Congress of the European Hematology Association (EHA) 2022, Copyright © 2022 The Author(s) [9].

Abstract Book for the 27th Congress of the European Hematology Association. Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the European Hematology Association [10].

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Data availability statement

The authors certify that this manuscript reports the primary analysis of clinical trial data that have been shared with them, and that the use of this shared data is in accordance with the terms (if any) agreed upon their receipt. The source of this data, including the redacted study protocol, redacted statistical analysis plan, and individual participants’ data supporting the results reported in this article, will be made available from the completed studies within three months from initial request, to researchers who provide a methodologically sound proposal. The data will be provided after its de-identification, in compliance with applicable privacy laws, data protection and requirements for consent and anonymization.