Patient characteristics phase 1/2 REPEAT study
| Characteristic . | Phase 1 (n = 21) . | Phase 2 (n = 61) . | Total (n = 82) . |
|---|---|---|---|
| Median age, y (range) | 69 (41-76) | 65 (43-82) | 66 (41-82) |
| Sex, male, n (%) | 16 (76) | 42 (69) | 58 (71) |
| Type of monoclonal heavy chain, n (%) | |||
| IgG | 11 (52) | 32 (52) | 43 (52) |
| IgA | 6 (29) | 8 (13) | 14 (17) |
| IgD | 0 (0) | 1 (2) | 1 (1) |
| Light chain only | 4 (19) | 20 (33) | 24 (29) |
| Type of light chain, n (%) | |||
| Kappa | 15 (71) | 39 (64) | 54 (66) |
| Lambda | 6 (29) | 22 (36) | 28 (34) |
| Median time from diagnosis until enrollment in months (range) | 41 (18-96) | 51 (5-169) | 48 (5-169) |
| Prior lines of therapy, median (range) | 3 (2-10) | 3 (1-6) | 3 (1-10) |
| Prior therapies, n (%) | |||
| Lenalidomide | 21 (100) | 67 (100) | 82 (100) |
| Bortezomib | 19 (90) | 52 (85) | 71 (87) |
| Thalidomide | 16 (76) | 36 (59) | 52 (63) |
| Cyclophosphamide | 10 (48) | 37 (61) | 47 (57) |
| Prior autologous stem cell transplantation (HDM) | 13 (62) | 37 (61) | 50 (61) |
| Oral melphalan | 11 (52) | 30 (49) | 41 (50) |
| Prior allogeneic stem cell transplantation | 3 (14) | 5 (8) | 8 (10) |
| Previous lenalidomide, n (%) | |||
| Refractory* | 21 (100) | 61 (100) | 82 (100) |
| Progression while on lenalidomide-containing therapy† | 19 (90) | 47 (77) | 66 (80) |
| No response during prior lenalidomide-based therapy‡ | 1 (5) | 4 (7) | 5 (6) |
| Progressive disease within 60 d after stopping lenalidomide-based therapy§ | 1 (5) | 10 (16) | 11 (14) |
| REP directly after development of lenalidomide-refractory disease | 13 (62) | 53 (87) | 66 (80) |
| Lenalidomide and bortezomib double refractory* | 16 (76) | 38 (62) | 54 (66) |
| International Staging System before start REP, n (%) | |||
| 1 | 7 (33) | 15 (27) | 22 (29) |
| 2 | 9 (43) | 25 (46) | 34 (45) |
| 3 | 5 (24) | 15 (27) | 20 (26) |
| WHO Performance Status, n (%) | |||
| 0 | 0 (0) | 10 (17) | 10 (12) |
| 1 | 15 (71) | 33 (56) | 48 (60) |
| 2 | 4 (19) | 11 (19) | 15 (19) |
| 3 | 2 (10) | 5 (8) | 7 (9) |
| β2-Microglobulin median, nmol/L (range) | 3.4 (1.7-10) | 3.4 (0.2-19.1) | 3.4 (0.2-19.1) |
| Laboratory values at baseline, median (range) | |||
| Absolute neutrophil count, ×109/L | 3.2 (1.2-20.5) | 2.6 (1.1-7.9) | 2.6 (1.1-20.5) |
| Hemoglobin, mM | 6.6 (5.3-9.2) | 6.9 (4.5-9.1) | 6.9 (4.5-9.2) |
| Platelet count, ×109/L | 183 (95-334) | 164 (50-369) | 167 (50-369) |
| Creatinine, μmol/L | 86 (58-117) | 86 (53-201) | 86 (53-201) |
| Calcium, mmol/L | 2.35 (2.15-2.64) | 2.31 (1.98-3.35) | 2.31 (1.98-3.35) |
| Cytogenetic abnormalities, n (%) | |||
| High risk|| | 10 (48) | 22 (36) | 32 (39) |
| Standard risk | 10 (48) | 20 (33) | 30 (37) |
| Not available | 1 (4) | 19 (31) | 20 (24) |
| Characteristic . | Phase 1 (n = 21) . | Phase 2 (n = 61) . | Total (n = 82) . |
|---|---|---|---|
| Median age, y (range) | 69 (41-76) | 65 (43-82) | 66 (41-82) |
| Sex, male, n (%) | 16 (76) | 42 (69) | 58 (71) |
| Type of monoclonal heavy chain, n (%) | |||
| IgG | 11 (52) | 32 (52) | 43 (52) |
| IgA | 6 (29) | 8 (13) | 14 (17) |
| IgD | 0 (0) | 1 (2) | 1 (1) |
| Light chain only | 4 (19) | 20 (33) | 24 (29) |
| Type of light chain, n (%) | |||
| Kappa | 15 (71) | 39 (64) | 54 (66) |
| Lambda | 6 (29) | 22 (36) | 28 (34) |
| Median time from diagnosis until enrollment in months (range) | 41 (18-96) | 51 (5-169) | 48 (5-169) |
| Prior lines of therapy, median (range) | 3 (2-10) | 3 (1-6) | 3 (1-10) |
| Prior therapies, n (%) | |||
| Lenalidomide | 21 (100) | 67 (100) | 82 (100) |
| Bortezomib | 19 (90) | 52 (85) | 71 (87) |
| Thalidomide | 16 (76) | 36 (59) | 52 (63) |
| Cyclophosphamide | 10 (48) | 37 (61) | 47 (57) |
| Prior autologous stem cell transplantation (HDM) | 13 (62) | 37 (61) | 50 (61) |
| Oral melphalan | 11 (52) | 30 (49) | 41 (50) |
| Prior allogeneic stem cell transplantation | 3 (14) | 5 (8) | 8 (10) |
| Previous lenalidomide, n (%) | |||
| Refractory* | 21 (100) | 61 (100) | 82 (100) |
| Progression while on lenalidomide-containing therapy† | 19 (90) | 47 (77) | 66 (80) |
| No response during prior lenalidomide-based therapy‡ | 1 (5) | 4 (7) | 5 (6) |
| Progressive disease within 60 d after stopping lenalidomide-based therapy§ | 1 (5) | 10 (16) | 11 (14) |
| REP directly after development of lenalidomide-refractory disease | 13 (62) | 53 (87) | 66 (80) |
| Lenalidomide and bortezomib double refractory* | 16 (76) | 38 (62) | 54 (66) |
| International Staging System before start REP, n (%) | |||
| 1 | 7 (33) | 15 (27) | 22 (29) |
| 2 | 9 (43) | 25 (46) | 34 (45) |
| 3 | 5 (24) | 15 (27) | 20 (26) |
| WHO Performance Status, n (%) | |||
| 0 | 0 (0) | 10 (17) | 10 (12) |
| 1 | 15 (71) | 33 (56) | 48 (60) |
| 2 | 4 (19) | 11 (19) | 15 (19) |
| 3 | 2 (10) | 5 (8) | 7 (9) |
| β2-Microglobulin median, nmol/L (range) | 3.4 (1.7-10) | 3.4 (0.2-19.1) | 3.4 (0.2-19.1) |
| Laboratory values at baseline, median (range) | |||
| Absolute neutrophil count, ×109/L | 3.2 (1.2-20.5) | 2.6 (1.1-7.9) | 2.6 (1.1-20.5) |
| Hemoglobin, mM | 6.6 (5.3-9.2) | 6.9 (4.5-9.1) | 6.9 (4.5-9.2) |
| Platelet count, ×109/L | 183 (95-334) | 164 (50-369) | 167 (50-369) |
| Creatinine, μmol/L | 86 (58-117) | 86 (53-201) | 86 (53-201) |
| Calcium, mmol/L | 2.35 (2.15-2.64) | 2.31 (1.98-3.35) | 2.31 (1.98-3.35) |
| Cytogenetic abnormalities, n (%) | |||
| High risk|| | 10 (48) | 22 (36) | 32 (39) |
| Standard risk | 10 (48) | 20 (33) | 30 (37) |
| Not available | 1 (4) | 19 (31) | 20 (24) |
HDM, high-dose melphalan.
Refractory disease is defined as progressive disease during therapy, no response (< PR), or progressive disease within 60 d of stopping treatment, according to the International Uniform Response Criteria for Multiple Myeloma.
Fifty patients progressed while receiving lenalidomide (25 mg)-dexamethasone, 6 while receiving lenalidomide, bortezomib, and dexamethasone, and 10 while receiving lenalidomide maintenance therapy (10 mg).
Three patients received lenalidomide (25 mg)-dexamethasone; 1 patient received 10 mg lenalidomide in MPR (melphalan, prednisone, lenalidomide), and 1 patient received lenalidomide (10 mg) maintenance therapy.
Ten patients received lenalidomide (25 mg)-dexamethasone, and 1 patient received 10 mg lenalidomide in MPR.
High-risk cytogenetic abnormalities were defined by the presence of t(4;14), t(14;16), del(17p), and/or ampl(1q) as determined by FISH analysis on purified MM cells before start of REP treatment. FISH analysis on purified MM cells was performed before the start of REP in 62 of 82 patients.