Why carry out this study?
|
Multiple myeloma (MM), a rare hematologic malignancy, led to 98,437 deaths and 2.1 million disability-adjusted life-years globally in 2016. Healthcare costs for newly diagnosed MM patients has risen over threefold from 2000 to 2014 in the United States. |
Although the American Society of Clinical Oncology guidelines recommend initiation of therapy with proteasome inhibitors, immunomodulators, and steroids for patients who are not eligible for autologous stem cell transplantation (ASCT), outcomes with these therapies are dependent on various factors. In addition, real-world studies evaluating the effects of these treatments are scarce. |
The present study evaluated the treatment patterns and outcomes among newly diagnosed MM patients who had not received ASCT, from the Surveillance, Epidemiology, and End Results (SEER)-Medicare and Optum databases. The study further compared the safety and clinical outcomes among different frontline regimens. |
What was learned from the study?
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The median OS of patients receiving Vd, VRd, CyBorD, and Rd therapy was 56.3 months, 112.6 months, 92.9 months, and 79.1 months, respectively. Patients treated with Rd therapy had the longest TTNT (24.3 months). |
The study demonstrated that the frontline therapies prescribed to the patients who did not receive ASCT for MM in the United States were consistent with NCCN guideline recommendations. Patients who had received VRd showed better outcomes compared with Rd, Vd, and CyBorD therapies. |
Digital Features
Introduction
Methods
Data Source
Study Design
Study Assessments
Statistical Analysis
Results
Baseline Characteristics
Bortezomib-containing n = 10,552 | Vd n = 4128 | VRd n = 2718 | CyBorD n = 1225 | Other bortezomib n = 2481 | Rd n = 4358 | Other n = 2821 | Overall n = 17,731 | |
---|---|---|---|---|---|---|---|---|
Age at index diagnosis (years, mean [SD]) | 70.7 (9.85) | 73.5 (9.44) | 68.7 (9.32) | 68.8 (9.47) | 69.4 (10.20) | 72.2 (9.71) | 71.6 (9.80) | 71.0 (9.83) |
Women [n (%)] | 5155 (48.85) | 2090 (50.62) | 1302 (47.90) | 531 (43.34) | 1232 (49.65) | 2193 (50.32) | 1431 (50.72) | 8779 (49.51) |
Diagnosis duration (months, mean [SD]) | 2.3 (6.9) | 2.9 (7.7) | 2.1 (7.0) | 1.5 (5.0) | 2 (5.8) | 3.7 (8.4) | 3 (7.0) | 2.8 (7.3) |
Insurance type (at LOT1 start) [n (%)] | ||||||||
Commercial | 2825 (26.77) | 771 (18.67) | 882 (32.45) | 419 (34.20) | 753 (30.35) | 1106 (25.37) | 744 (26.37) | 4675 (26.36) |
Medicare | 6187 (58.63) | 2922 (70.78) | 1417 (52.13) | 653 (53.30) | 1195 (48.16) | 2527 (57.98) | 1504 (53.31) | 10,218 (57.62) |
Medicaid | 264 (2.50) | 83 (2.01) | 60 (2.20) | 42 (3.42) | 79 (3.18) | 64 (1.46) | 52 (1.84) | 380 (2.14) |
Other/unknown/missing | 1276 (12.09) | 352 (8.52) | 359 (13.20) | 111 (9.06) | 454 (18.29) | 661 (15.16) | 521 (18.46) | 2458 (13.86) |
Charlson comorbiditya (mean [SD]) | 2.1 (2.4) | 2.6 (2.6) | 1.6 (2.2) | 2.2 (2.3) | 1.6 (2.2) | 1.6 (2.2) | 1.5 (2.1) | 1.9 (2.3) |
Baseline comorbidities* [n (%)] | ||||||||
Hypertension | 6670 (63.21) | 2914 (70.59) | 1592 (58.57) | 848 (69.22) | 1316 (53.04) | 2460 (56.44) | 1487 (52.71) | 10,617 (59.87) |
Renal failure | 3723 (35.28) | 1760 (42.63) | 666 (24.50) | 552 (45.06) | 745 (30.02) | 967 (22.18) | 725 (25.70) | 5415 (30.53) |
Fluid and electrolyte disorders | 3384 (32.06) | 1484 (35.94) | 666 (24.50) | 497 (40.57) | 737 (29.70) | 865 (19.84) | 598 (21.19) | 4847 (27.33) |
Diabetes | 2846 (26.97) | 1248 (30.23) | 708 (26.04) | 362 (29.55) | 528 (21.28) | 1058 (24.27) | 596 (21.12) | 4500 (25.37) |
Cardiac arrhythmia | 2585 (24.49) | 1155 (27.97) | 512 (18.83) | 349 (28.48) | 569 (22.98) | 912 (20.92) | 597 (21.16) | 4094 (23.08) |
Chronic pulmonary disease | 2122 (20.10) | 915 (22.16) | 447 (16.44) | 279 (22.77) | 481 (19.38) | 672 (15.41) | 495 (17.54) | 3289 (18.54) |
Deficiency anemia | 2067 (19.58) | 969 (23.47) | 495 (18.21) | 266 (21.71) | 337 (13.58) | 630 (14.45) | 386 (13.68) | 3083 (17.38) |
Congestive heart failure | 1953 (18.50) | 901 (21.82) | 336 (12.36) | 309 (25.22) | 407 (16.40) | 567 (13.01) | 433 (15.34) | 2953 (16.65) |
Hypothyroidism | 1628 (15.42) | 732 (17.73) | 364 (13.39) | 196 (16.00) | 336 (13.54) | 639 (14.66) | 376 (13.32) | 2643 (14.90) |
Valvular disease | 1480 (14.02) | 676 (16.37) | 279 (10.26) | 223 (18.20) | 302 (12.17) | 438 (10.05) | 347 (12.30) | 2265 (12.77) |
Peripheral neuropathy | 1241 (11.76) | 574 (13.90) | 268 (9.86) | 163 (13.30) | 236 (9.51) | 462 (10.60) | 276 (9.78) | 1979 (11.16) |
Frontline comorbidities [n (%)] | ||||||||
Anemia | 6187 (58.63) | 2528 (61.24) | 1624 (59.74) | 758 (61.87) | 1277 (51.47) | 1956 (44.88) | 1193 (42.28) | 9336 (52.65) |
Thrombocytopenia | 1109 (10.50) | 334 (8.09) | 340 (12.50) | 145 (11.88) | 290 (11.68) | 262 (6.01) | 170 (6.02) | 1541 (8.69) |
Neutropenia | 974 (9.23) | 262 (6.34) | 324 (11.92) | 124 (10.12) | 264 (10.64) | 372 (8.53) | 234 (8.29) | 1580 (8.91) |
Peripheral neuropathy | 2296 (21.75) | 922 (22.33) | 734 (27.00) | 223 (18.20) | 417 (16.80) | 726 (16.65) | 460 (16.30) | 3482 (19.63) |
With history | 4075 (38.61) | 1530 (37.06) | 1216 (44.73) | 424 (34.61) | 919 (37.04) | 1481 (33.98) | 1039 (36.83) | 6607 (37.26) |
Without history | 1697 (16.08) | 668 (16.18) | 584 (21.48) | 153 (12.48) | 297 (11.97) | 494 (11.33) | 319 (11.30) | 2501 (14.10) |
Diarrhea | 1683 (15.94) | 665 (16.10) | 550 (20.23) | 163 (13.30) | 305 (12.29) | 528 (12.11) | 246 (8.72) | 2457 (13.85) |
Nausea | 3198 (30.30) | 1301 (31.51) | 921 (33.88) | 373 (30.44) | 603 (24.30) | 845 (19.38) | 423 (14.99) | 4466 (25.18) |
Fatigue | 2455 (23.26) | 1154 (27.95) | 593 (21.81) | 225 (18.36) | 483 (19.46) | 909 (20.85) | 534 (18.92) | 3898 (21.98) |
Hematological malignancy | 816 (7.73) | 367 (8.89) | 236 (8.68) | 79 (6.44) | 134 (5.40) | 280 (6.42) | 128 (4.53) | 1224 (6.90) |
Solid tumors | 978 (9.26) | 428 (10.36) | 294 (10.81) | 88 (7.18) | 168 (6.77) | 383 (8.78) | 191 (6.77) | 1552 (8.75) |
Infusion related reactions | 284 (2.69) | 132 (3.19) | 82 (3.01) | 17 (1.38) | 53 (2.13) | 84 (1.92) | 55 (1.94) | 423 (2.38) |
Frontline Comorbidities
Treatment Duration and Treatment Switch
Bortezomib-containing n = 10,552 | Vd n = 4128 | VRd n = 2718 | CyBorD n = 1225 | Other bortezomib n = 2481 | Rd n = 4358 | Other n = 2821 | Overall n = 17,731 | |
---|---|---|---|---|---|---|---|---|
Treatment duration (in days)* | ||||||||
Mean (SD) | 196.3 (241.6) | 191.2 (215.2) | 282.9 (321.0) | 153 (153.5) | 143.8 (209.5) | 258.8 (345.1) | 166.6 (246.7) | 206.5 (272.6) |
Median (Q1-Q3) | 124 (57–226) | 129 (66–226) | 181 (95–345) | 121 (65–187) | 69 (38–156) | 121 (38–322) | 75 (31–192) | 116 (47–238) |
Treatment-free interval (TFI) | ||||||||
Mean (SD) | 119 (282.3) | 165.1 (335.2) | 101.6 (254.0) | 74.6 (191.5) | 83.1 (238.9) | 160.6 (317.4) | 145.1 (323.1) | 133.3 (298.5) |
Median (Q1-Q3) | 1 (1–99) | 8 (1–183) | 1 (1–75) | 1 (1–61) | 1 (1–46) | 13 (1–189) | 11 (1–141) | 1 (1–127) |
Patients received subsequent therapy (LOT2) | ||||||||
n | 4842 | 1860 | 1013 | 719 | 1250 | 1580 | 1187 | 7609 |
% (percentages are based on LOT1) | 45.88% | 45.05% | 37.27% | 58.69% | 50.38% | 36.25% | 42.07% | 42.91% |
Bortezomib mono | ||||||||
n | 290 | 84 | 52 | 101 | 53 | 117 | 58 | 465 |
% switched from LOT1 | 5.98% | 4.51% | 5.13% | 14.04% | 4.24% | 7.40% | 4.88% | 6.11% |
Treatment duration (in days)a | ||||||||
Mean (SD) | 210 (303.3) | 284.3 (417.9) | 124.8 (103.1) | 221.7 (291.2) | 148 (178.7) | 181.8 (186.3) | 138.1 (153.7) | 192 (259.6) |
Median (Q1-Q3) | 110 (58–230) | 165.5 (68.5–307) | 103 (51–172.5) | 125 (77–238) | 73.5 (39–155) | 119.5 (61–235) | 90 (42–170) | 109.5 (56–223.5) |
Bortezomib combination regimens | ||||||||
n | 1241 | 476 | 183 | 205 | 377 | 374 | 243 | 1858 |
% switched from LOT1 | 25.62% | 25.59% | 18.06% | 28.51% | 30.16% | 23.67% | 20.47% | 24.41% |
Treatment duration (in days)a | ||||||||
Mean (SD) | 167.4 (172.1) | 168.9 (166.8) | 150.5 (147.4) | 157.7 (170.6) | 177.7 (188.4) | 222.8 (234.9) | 192.7 (212.8) | 181.7 (192.8) |
Median (Q1-Q3) | 105.5 (59–208) | 118 (61–212) | 97 (56–175) | 91 (57–204) | 100 (59–230) | 153 (90–247) | 128 (65–219) | 119 (63–221) |
Lenalidomide mono | ||||||||
n | 335 | 185 | 59 | 36 | 55 | 139 | 93 | 567 |
% switched from LOT1 | 6.90% | 9.94% | 5.82% | 5.00% | 4.40% | 8.79% | 7.83% | 7.54% |
Treatment duration (in days)a | ||||||||
Mean (SD) | 247.6 (323.1) | 212.4 (308.9) | 246.7 (260.5) | 329.5 (384.4) | 311.8 (366.4) | 158.4 (193.7) | 254.2 (379.1) | 225.9 (308.3) |
Median (Q1-Q3) | 113 (31–337) | 94 (30–212) | 132 (30–437.5) | 268.5 (68–382) | 119.5 (70–522.5) | 67 (30–211) | 108 (38–254) | 106 (30–260) |
Lenalidomide combination regimens | ||||||||
n | 763 | 379 | 122 | 86 | 176 | 313 | 316 | 1392 |
% switched from LOT1 | 15.75% | 20.37% | 12.04% | 11.96% | 14.08% | 19.81% | 26.62% | 18.29% |
Treatment duration (in days)a | ||||||||
Mean (SD) | 277.2 (314.4) | 313.8 (339.4) | 219.5 (248.7) | 260.9 (238.6) | 245.6 (321.8) | 264.4 (317.4) | 264.4 (348.3) | 271.2 (323.2) |
Median (Q1-Q3) | 166.5 (78–339) | 204 (86–394) | 114 (56–271) | 155.5 (88–353.5) | 129 (75–250) | 139 (44–361) | 130.5 (61–314) | 154 (68–340) |
Other regimens | ||||||||
n | 2213 | 736 | 597 | 291 | 589 | 637 | 477 | 3327 |
% switched from LOT1 | 45.70% | 39.56% | 58.93% | 40.47% | 47.12% | 40.31% | 40.18% | 43.72% |
Treatment duration (in days)a | ||||||||
Mean (SD) | 206.8 (258) | 243.1 (268.6) | 173.4 (214.3) | 177.1 (194.5) | 209.2 (302.4) | 234.6 (311.3) | 209.1 (280.3) | 212.2 (272.1) |
Median (Q1-Q3) | 113 (52–253) | 154 (62–310) | 94 (47–219) | 92 (49–208) | 102 (55–224) | 127 (58–281) | 101 (46–246) | 113 (52–256) |
Overall Survival
Parameters | VRd vs. Vd | VRd vs. CyBorD | VRd vs. other bortezomib | VRd vs. Rd | VRd vs. other | |||||
---|---|---|---|---|---|---|---|---|---|---|
HR (95% CI) | P value | HR (95% CI) | P value | HR (95% CI) | P value | HR (95% CI) | P value | HR (95% CI) | P value | |
OS | ||||||||||
PSM | 0.76 (0.66, 0.86) | < 0.0001 | 0.87* (0.72, 1.05) | 0.1548 | 0.56 (0.49, 0.64) | < 0.0001 | 0.83 (0.73, 0.95) | 0.0072 | 0.70 (0.61, 0.80) | < 0.0001 |
Multivariate analysis | 0.79 (0.71, 0.86) | < 0.0001 | 0.90* (0.78, 1.02) | 0.1212 | 0.63 (0.57, 0.70) | < 0.0001 | 0.92* (0.83, 1.01) | 0.1003 | 0.74 (0.67, 0.82) | < 0.0001 |
Imputed OS | ||||||||||
PSM | 0.78 (0.70, 0.86) | < 0.0001 | 0.78 (0.68, 0.91) | 0.0017 | 0.58 (0.52, 0.65) | < 0.0001 | 0.74 (0.67, 0.81) | < 0.0001 | 0.69 (0.62, 0.76) | < 0.0001 |
Multivariate analysis | 0.82 (0.76, 0.88) | < 0.0001 | 0.79 (0.72, 0.87) | < 0.0001 | 0.66 (0.61, 0.72) | < 0.0001 | 0.81 (0.75, 0.87) | < 0.0001 | 0.69 (0.64, 0.74) | < 0.0001 |
TTNT | ||||||||||
PSM | 0.57 (0.50, 0.65) | < 0.0001 | 0.28 (0.23, 0.34) | < 0.0001 | 0.27 (0.23, 0.32) | < 0.0001 | 0.97* (0.84, 1.11) | 0.6752 | 0.54 (0.47, 0.63) | < 0.0001 |
Multivariate analysis | 0.68 (0.63, 0.74) | < 0.0001 | 0.34 (0.30, 0.37) | < 0.0001 | 0.40 (0.37, 0.44) | < 0.0001 | 1.05* (0.96, 1.14) | 0.2411 | 0.66 (0.61, 0.73) | < 0.0001 |
Time to Next Treatment (TTNT) and Treatment-Free Interval (TFI)
Association Between Frontline Treatment Duration and Outcomes
HR (CI) | OS | Imputed OS | TTNT | ||||||
---|---|---|---|---|---|---|---|---|---|
Base case | Sensitivity analyses 1 | Sensitivity analyses 2 | Base case | Sensitivity analyses 1 | Sensitivity analyses 2 | Base case | Sensitivity analyses 1 | Sensitivity analyses 2 | |
Overall | 0.86 (0.82, 0.90) | 0.67 (0.64, 0.70) | 0.73 (0.70, 0.77) | 0.58 (0.56, 0.61) | 0.42 (0.4, 0.43) | 0.47 (0.45, 0.49) | 1.04 (0.99, 1.1) | 0.43 (0.41, 0.45) | 0.64 (0.61, 0.67) |
Bortezomib-containing | 0.81 (0.76, 0.86) | 0.61 (0.57, 0.65) | 0.67 (0.63, 0.71) | 0.58 (0.55, 0.61) | 0.40 (0.38, 0.42) | 0.46 (0.44, 0.48) | 1.21 (1.13, 1.29) | 0.42 (0.39, 0.44) | 0.67 (0.63, 0.71) |
Vd | 0.81 (0.74, 0.89) | 0.61 (0.55, 0.67) | 0.67 (0.61, 0.74) | 0.62 (0.57, 0.67) | 0.43 (0.4, 0.47) | 0.50 (0.46, 0.54) | 1.33 (1.21, 1.47) | 0.53 (0.48, 0.58) | 0.81 (0.74, 0.89) |
VRd | 0.87 (0.74, 1.01) | 0.59 (0.51, 0.69) | 0.70 (0.6, 0.81) | 0.57 (0.51, 0.64) | 0.34 (0.31, 0.39) | 0.43 (0.38, 0.48) | 1.20 (1.05, 1.39) | 0.36 (0.32, 0.41) | 0.66 (0.58, 0.75) |
CyBorD | 0.79 (0.64, 0.98) | 0.59 (0.48, 0.73) | 0.66 (0.54, 0.81) | 0.60 (0.52, 0.71) | 0.41 (0.35, 0.47) | 0.48 (0.41, 0.56) | 2.11 (1.8, 2.48) | 0.47 (0.4, 0.55) | 1.02 (0.88, 1.19) |
Other bortezomib | 1.11 (0.98, 1.25) | 0.91 (0.81, 1.03) | 0.97 (0.86, 1.09) | 0.63 (0.57, 0.7) | 0.48 (0.44, 0.53) | 0.53 (0.48, 0.58) | 1.12 (0.98, 1.27) | 0.40 (0.36, 0.45) | 0.61 (0.55, 0.69) |
Rd | 0.86 (0.78, 0.95) | 0.69 (0.62, 0.76) | 0.75 (0.68, 0.83) | 0.60 (0.56, 0.65) | 0.43 (0.4, 0.46) | 0.49 (0.45, 0.52) | 0.68 (0.61, 0.76) | 0.37 (0.33, 0.41) | 0.49 (0.44, 0.54) |
Other | 1.04 (0.93, 1.16) | 0.90 (0.81, 1.01) | 0.95 (0.85, 1.06) | 0.62 (0.57, 0.68) | 0.49 (0.45, 0.54) | 0.53 (0.49, 0.58) | 1.07 (0.94, 1.21) | 0.59 (0.52, 0.67) | 0.77 (0.68, 0.87) |