Lenalidomide in Combination with Dexamethasone Was More Effective Than Dexamethasone in Patients Who Have Received Prior Thalidomide for Relapsed or Refractory Multiple Myeloma.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 3553-3553 ◽  
Author(s):  
Michael Wang ◽  
Robert Knight ◽  
Melitios Dimopoulos ◽  
David Siegel ◽  
S. Vincent Rajkumar ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Remission Rate ◽  
Phase Iii ◽  
Cross Resistance ◽  
Time To Progression ◽  
Double Blind ◽  
Refractory Multiple Myeloma ◽  
Hazards Model ◽  
Phase Iii Trials ◽  
Beta 2 Microglobulin

Abstract Lenalidomide (Len), an analog of thalidomide (thal) is a novel, oral, immunomodulatory agent that is effective against multiple myeloma (MM). In 2 prospective, randomized, double-blind, placebo-controlled Phase III trials. Len with dexamethasone (Dex) induced a significantly higher overall response rate (OR) and complete remission rate (CR), as well as longer time-to-progression (TTP) in comparison with Dex alone. This prospective analysis assessed whether prior thalidomide exposure might induce subsequent resistance to Len/Dex. We evaluated 704 patients (pts) from both trials (MM009, MM010) who had relapsed or refractory multiple myeloma, had not been resistant to Dex and were randomized to receive either oral Len (25 mg daily for 3 weeks every 4 weeks) plus Dex (40 mg on days 1–4, 9–12, 17–20 every 4 weeks for 4 cycles) or placebo plus Dex. Two hundred seventy four pts (39%) received prior thal, while 430 (61%) had not. The prior thal exposed pts and thal-naive pts were similar in regard to age, Beta-2-microglobulin, hemoglobin, serum M protein, albumin and history of previous transplantation. The frequency of deep venous thrombosis and pulmonary embolism (DVT/PE) with prior thal exposure was higher at 14% with Len/Dex than 4% with Dex alone (p < 0.01). However, the frequency of DVT/PE with no prior thal exposure was similar at 8% with Len/Dex to 6% with Dex alone (p = 0.49). In the prior thal pts, severe neuropathy occurred in 4% with Len/Dex, not significantly different from the 1% with Dex alone (p=0.2). The pooled data from all 704 pts showed that pts treated with Len/Dex, compared with those treated with Dex alone, had superior median Time-To-Progression (TTP) (48 vs 20 weeks) and OR (60% vs 22%, p <0.001). Similarly, among the subgroups exposed or not exposed to thal, Len/Dex was superior to Dex alone in OR and TTP. For the 126 patients who received prior thal, the OR with Len/Dex was significantly less (43%) among 54 Pts resistant to thal than that observed for 72 Pts who had been sensitive to thal (63%, p < 0.05). Multivariate analysis using Cox proportion hazards model indicated that after controlling for treatment (Len/Dex vs Dex) and baseline disease characteristics, independent and significant predictors of shorter TTP included prior thal exposure, duration of myeloma and number of prior therapies. Len in combination with Dex was more effective than Dex in patients with relapsed or refractory multiple myeloma despite prior thal exposure. Results with Len/Dex were superior for those not exposed to thal, suggesting some, but not complete, cross resistance between Len and thal. Len/Dex vs Dex with or without Prior Thal Thal (N=274) No Thal (N=430) LD D p LD D p Intent-to-Treat (n) 126 148 227 203 TTP (med. weeks) 36.9 19.9 <.001 61.3 20.4 <.001 OR (%) 54.0 14.9 <.001 63.4 27.6 <.001 PR (%) 42.1 12.8 <.001 32.2 23.2 <.05 NCR (%) 4.0 0.7 <.001 13.2 2.0 <.001 CR (%) 7.9 1.4 <.01 18.1 2.5 <.001

Randomized Phase III Study of Pegylated Liposomal Doxorubicin Plus Bortezomib Compared With Bortezomib Alone in Relapsed or Refractory Multiple Myeloma: Combination Therapy Improves Time to Progression

2007 ◽  
Vol 25 (25) ◽  
pp. 3892-3901 ◽  
Author(s):  
Robert Z. Orlowski ◽  
Arnon Nagler ◽  
Pieter Sonneveld ◽  
Joan Bladé ◽  
Roman Hajek ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Combination Therapy ◽  
Liposomal Doxorubicin ◽  
Pegylated Liposomal Doxorubicin ◽  
International Study ◽  
Phase Iii ◽  
Combination Group ◽  
Time To Progression ◽  
Refractory Multiple Myeloma ◽  
Grade 3

PurposeThis phase III international study compared the efficacy and safety of a combination of pegylated liposomal doxorubicin (PLD) plus bortezomib with bortezomib monotherapy in patients with relapsed or refractory multiple myeloma.Patients and MethodsSix hundred forty-six patients were randomly assigned to receive either intravenous bortezomib 1.3 mg/m2on days 1, 4, 8, and 11 of an every 21-days cycle, or the same bortezomib regimen with PLD 30 mg/m2on day 4.ResultsMedian time to progression was increased from 6.5 months for bortezomib to 9.3 months with the PLD + bortezomib combination (P = .000004; hazard ratio, 1.82 [monotherapy v combination therapy]; 95% CI, 1.41 to 2.35). The 15-month survival rate for PLD + bortezomib was 76% compared with 65% for bortezomib alone (P = .03). The complete plus partial response rate was 41% for bortezomib and 44% for PLD + bortezomib, a difference that was not statistically significant. Median duration of response was increased from 7.0 to 10.2 months (P = .0008) with PLD + bortezomib. Grade 3/4 adverse events were more frequent in the combination group (80% v 64%), with safety profiles consistent with the known toxicities of the two agents. An increased incidence in the combination group was seen of grade 3/4 neutropenia, thrombocytopenia, asthenia, fatigue, diarrhea, and hand-foot syndrome.ConclusionPLD with bortezomib is superior to bortezomib monotherapy for the treatment of patients with relapsed or refractory multiple myeloma. The combination therapy is associated with a higher incidence of grade 3/4 myelosuppression, constitutional symptoms, and GI and dermatologic toxicities.

Effect of Disease Stage and Time Since Diagnosis on Time to Progression for Pegylated Liposomal Doxorubicin + Bortezomib vs Bortezomib Alone in Relapsed or Refractory Multiple Myeloma.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 2740-2740
Author(s):  
Heather J. Sutherland ◽  
Joan Blade ◽  
Jesus San Miguel ◽  
Arnon Nagler ◽  
Pieter Sonneveld ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Liposomal Doxorubicin ◽  
Pegylated Liposomal Doxorubicin ◽  
Staging System ◽  
Risk Groups ◽  
Phase Iii ◽  
Disease Stage ◽  
Time To Progression ◽  
Total Study Population ◽  
Refractory Multiple Myeloma

Abstract A recent report of a phase III randomized trial with pegylated liposomal doxorubicin (PLD)+bortezomib vs. bortezomib alone in relapsed or refractory multiple myeloma (RRMM) demonstrated improved time to progression (TTP) with PLD+bortezomib (Orlowski, JCO 2007). The present post-hoc analyses evaluated the efficacy of PLD+bortezomib according to International Staging System (ISS) disease stage, and time since initial myeloma diagnosis (TSD). Patients with ≥1 prior therapy were randomized to receive PLD at 30 mg/m2 on day 4 and bortezomib at 1.3 mg/m2 on days 1, 4, 8, and 11, or bortezomib alone for up to eight 21-day cycles, or at least 2 cycles beyond CR, or optimal response unless disease progression or unacceptable toxicities occurred. The improved TTP reported previously with PLD+bortezomib over bortezomib alone in the total study population was also observed in the higher risk groups based on disease stage (ISS 2 & 3; Table). TTP was also significantly longer with PLD+bortezomib vs. bortezomib for TSD >2 yrs despite more protracted disease. The therapeutic advantage of prolonged TTP with the PLD+bortezomib combination was maintained consistently across subgroups (heterogeneity tests: ISS 1 vs. 2 vs. 3, p=0.407; TSD ≤2 yrs. vs. >2 yrs., p=0.946). Incidence of grade 3/4 neuropathies was low (<10%) in the two treatment arms in all subgroups. PLD-related hand-foot syndrome was also <10% in all PLD+bortezomib subgroups. Despite high-grade disease or protracted disease history, the PLD+bortezomib combination shows significantly improved TTP as compared to bortezomib alone. Also, the combination therapy was well-tolerated.

Lenalidomide/Dexamethasone Improves Response and Prolongs Time to Progression, Even in Patients with IgA Multiple Myeloma: A Sub-Analysis of the MM-009/010 Studies.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 4839-4839 ◽  
Author(s):  
Robert Foa ◽  
Donna Weber ◽  
Meletios Dimopoulos ◽  
Marta Olesnyckyj ◽  
Zhinuan Yu ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Adverse Events ◽  
Response Rate ◽  
Complete Response ◽  
High Response Rate ◽  
Response To Therapy ◽  
Phase Iii ◽  
Time To Progression ◽  
Phase Iii Trials ◽  
The Impact

Abstract Background: Historically, patients with IgA multiple myeloma (MM) respond poorly to treatment. In 2 recent phase III trials, Lenalidomide (Len) in combination with Dexamethasone (Dex) led to an overall response (OR) rate of approximately 60% (61% in MM-009 and 60% in MM-010), a complete response (CR) rate of about 15% (14% and 16%, respectively), an overall survival (OS) of at least 29.5 months (29.5 and not yet reached), and a median time to progression (TTP) of at least 11.1 months (11.1 months and 11.3 months, respectively) in patients with relapsed/refractory MM. In both studies, OR, CR, OS and TTP were significantly better with Len/Dex than with Dex alone. Here, we assess the impact of IgA disease on the efficacy and tolerability of treatment with Len/Dex versus Dex alone. Methods: Data were pooled from the MM-009 and MM-010 studies. Patients were randomized to receive Len (25 mg/day on days 1–21 of each 28-day cycle) or placebo. Both groups received Dex 40mg PO q.d. on days 1–4, 9–12, and 17–20 (for the first four cycles). After four cycles, Dex 40 mg/day was administered only on days 1–4. Response to therapy, TTP, OS, and adverse events were assessed. Response rate and TTP were based on data obtained before unblinding (June 2005 [MM-009] and August 2005 [MM-010]). Results: Of 154 patients with IgA at baseline, 72 were treated with Len/Dex and 82 with Dex alone. Among those without IgA, 281 received Len/Dex and 269 received Dex alone. Baseline characteristics were balanced between treatment groups. Len/Dex was associated with a significantly higher OR and longer median TTP than Dex alone in patients with and without IgA (Table). In the non-IgA group, patients treated with Len/Dex had a significantly longer OS than those treated with Dex alone. Response, TTP and OS were comparable between IgA and non-IgA patient groups. There was no difference in the incidence of adverse events between patients with and without IgA. Among those with IgA, the most common grade 3–4 adverse events with Len/Dex and Dex alone were neutropenia (37.5% and 2.4%), thrombocytopenia (16.7% and 8.5%), and anemia (11.1% and 7.3%). The respective rates for patients without IgA were 46.5% and 14.5%, 12.1% and 5.7%, and 11.0% and 5.7%. Conclusion: In patients with and in those without IgA MM, Len/Dex treatment induces a high response rate and a prolonged TTP compared with Dex. IgA non-IgA Clinical response, % Len/Dex (n=72) Dex alone (n=82) P Len/Dex (n=281) Dex alone (n=269) P OR 68.1 18.3 <0.001 57.7 23.0 <0.001 CR 18.1 0 NS 14.2 2.6 NS PR 38.9 15.9 NS 35.6 19.3 NS Median TTP, wks 44.3 16.4 <0.001 52.1 20.1 <0.001 Median OS, wks 130.4 102.4 NS 156.0 136.1 <0.05

Prolonged Overall Survival with Lenalidomide Plus Dexamethasone Compared with Dexamethasone Alone in Patients with Relapsed or Refractory Multiple Myeloma.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 412-412 ◽  
Author(s):  
Donna Weber ◽  
Robert Knight ◽  
Christine Chen ◽  
Andrew Spencer ◽  
Zhinuan Yu ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Overall Survival ◽  
Prior Treatment ◽  
Phase Iii ◽  
P Value ◽  
Double Blind ◽  
Prior Therapy ◽  
Phase Iii Trials

Abstract Introduction: Lenalidomide (Len), an analog of thalidomide (Thal) is a novel, oral, immunomodulatory agent that is effective against multiple myeloma (MM). In 2 prospective, randomized, double-blind, placebo-controlled phase III trials, Len with dexamethasone (Dex) induced a significantly higher overall response (OR) rate and complete remission (CR) rate, as well as longer time-to-progression (TTP) in comparison with Dex alone. Here, we investigate the long-term overall survival (OS) with Len/Dex. Methods: We evaluated the pooled results from both randomized trials (MM-009, MM-010) of 704 patients who had relapsed or refractory MM, without prior resistance to Dex, who received either Len (25 mg daily for 3 weeks every 4 weeks), or placebo. Dex was given at 40 mg on days 1–4, 9–12, 17–20 every 4 weeks for 4 cycles. From cycle 5 onwards, Dex was given at 40 mg on days 1–4 only. Response rate and TTP are based on data obtained before unblinding (June 2005 [MM-009] and August 2005 [MM-010]). Follow-up data on OS were obtained up to January 2007. Forty-seven percent of patients who received placebo/Dex crossed over to receive Len +/− Dex. Results: Of 704 patients, 353 were treated with Len/Dex and 351 with Dex alone. Baseline characteristics were well balanced between patients receiving Len/Dex and those receiving Dex alone. Median TTP, OR, and CR were significantly improved in patients treated with Len/Dex compared with Dex alone (Table). Of patients who progressed on Dex alone prior to unblinding, or were found to be receiving Dex alone after unblinding, 47% crossed over to Len +/− Dex. Despite these patients crossing over to Len +/− Dex at progression or at the time of unblinding, the OS was significantly improved in patients treated with Len/Dex compared with Dex alone (hazard ratio 1.295; 95% confidence interval 1.040–1.614; p=0.02). Median OS in the Len/Dex group was 35 months and 31 in the Dex alone group (p<0.05). Median OS was also significantly longer with Len/Dex compared with Dex alone in patients with more than 1 prior therapy (32.4 months versus 27.3 months, p<0.05). Similar median OS was observed with Len/Dex and Dex alone in patients with 1 prior therapy (median OS not yet reached and 35.3 months, p=0.24). Conclusion: With increased follow-up and despite cross-over, patients treated first with Len/Dex had significantly improved OS compared with those treated with Dex alone. Len/Dex (n=353) Dex alone (n=351) P value OR, % 60.6 21.9 <0.001 CR, % 15.0 2.0 <0.001 Median TTP, months 11.2 4.7 <0.001 Median OS, months 35.0 31.0 <0.05 Median OS in patients with 1 prior treatment, months not yet reached 35.3 0.24 Median OS in patients with >1 prior treatment, months 32.4 27.3 <0.05

The Effect of Bone Marrow Involvement on the Efficacy of Pegylated Liposomal Doxorubicin + Bortezomib Vs Bortezomib Alone in Patients with Relapsed/Refractory Multiple Myeloma

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 5192-5192
Author(s):  
Jatin Shah ◽  
Joan Blade ◽  
Jesus San Miguel ◽  
Pieter Sonneveld ◽  
Donghan Luo ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Liposomal Doxorubicin ◽  
Bone Marrow Involvement ◽  
Pegylated Liposomal Doxorubicin ◽  
Tumor Burden ◽  
Phase Iii ◽  
Rank Test ◽  
Time To Progression ◽  
Refractory Multiple Myeloma

Abstract Background: Patients with relapsed/refractory multiple myeloma (RRMM) often have a large tumor burden with significant bone marrow involvement, conferring a poor prognostic feature. Those patients with significant bone marrow involvement may benefit from combination regimens with increased activity. Orlowski et al. reported a phase III randomized trial with pegylated liposomal doxorubicin (PLD) + bortezomib (B) vs. B alone in RRMM, which demonstrated improved time to progression (TTP) with the combination of PLD+B. (Orlowski, JCO 2007) We investigated the effect of bone marrow involvement on overall response rates and time to progression (TTP) of PLD+ B versus B alone in patients with RRMM. Methods: Eligible patients were randomized to bolus IV B 1.3 mg/m2 on days 1, 4, 8, and 11 of each 3-week cycle (n=322) or to the same B regimen plus IV PLD 30 mg/m2 on day 4 (n=324) of each cycle. The subsets of patients with bone marrow involvement and those with &gt;30% involvement were analyzed retrospectively. Results: A total of 379 patients had bone marrow involvement and 349 patients had &gt;30% bone marrow involvement compared with 259 with no bone marrow involvement. Time to disease progression (TTP) and complete response (CR) + partial response (PR) rates for PLD+B vs B alone in patients with or without any bone marrow involvement or &gt;30% bone marrow involvement are listed in the table. PLD+B B P valueb Hazard Ratioc a. Based on Kaplan-Meier product-limit estimates. b. Based on stratified Log-rank test. c. A hazard ratio &gt;1 indicates an advantage for PLD+B. d. Cochran-Mantel-Haenszel test controlling for Beta2 microglobulin and response to initial treatment. No bone marrow involvement, N 132 127 TTP, Median days (95% CI)a 251 (212, 282) 198 (162, 227) 0.0134 1.69 (1.11, 2.57) Total CR+PR, n/evaluable (%) 49/118 (42) 43/124 (35) 0.2887d Any bone marrow involvement, N 188 191 TTP 311 (264, 354) 197 (169, 222) .0001 1.91 (1.37, 2.67) Total CR+PR 94/183 (51) 88/182 (48) .5187d &gt;30% bone marrow involvement, N 172 177 TTP 276 (221, 415) 183 (158, 211) .0005 1.83 (1.30, 2.58) Total CR+PR 82/168 (49) 69/170 (41) .1446d Regardless of bone marrow involvement or extent of bone marrow involvement, there was a statistically significant benefit in TTP for PLD+B vs. B alone. Safety profiles for the 2 regimens in the subsets of patients with or without bone marrow involvement were consistent with the known toxicities of the 2 agents. Conclusions: These data suggest that the combination of PLD+B is an active salvage therapy and superior to B alone in patients with RRMM, regardless of the presence or extent of bone marrow involvement. Patients with significant bone marrow involvement and associated poor risk due to increased tumor burden may benefit from the addition of PLD.

Comparison of lenalidomide in combination with dexamethasone to dexamethasone alone in patients who have received prior thalidomide in relapsed or refractory multiple myeloma

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 7522-7522 ◽  
Author(s):  
M. Wang ◽  
R. Knight ◽  
M. Dimopoulos ◽  
D. Siegel ◽  
S. V. Rajkumar ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Subgroup Analysis ◽  
Phase Iii ◽  
Significant Variable ◽  
Refractory Multiple Myeloma ◽  
Prior Therapy ◽  
Pooled Data ◽  
Phase Iii Trials ◽  
Previously Treated ◽  
The Impact

7522 Background: Lenalidomide (len), an analog of thalidomide (thal) is a novel, oral immunomodulatory agent that is effective against multiple myeloma (MM). Two randomized, Phase III trials (MM009 and MM010) have recently demonstrated superior responses and overall survival (OS) for patients (pts) treated with len and dexamethasone (dex) in comparison with dex-placebo. This is a prospective subgroup analysis to assess the impact of prior therapy with thal on the sensitivity of MM to subsequent lenalidomide. Methods: We evaluated 692 pts from both trials (MM009 and MM010). The pts had relapsed/refractory MM, were not refractory to dex and were randomized to receive either len (25 mg daily for 3 weeks (wks) every 4 wks) plus dex (40 mg on days 1–4, 9–12, 17–20 every 4 wks for 4 cycles, then 40 mg on days 1–4 every subsequent cycle) or placebo plus dex. Standard criteria were used to evaluate response and TTP. Results: Pooled data from 692 pts showed superior median TTP (48.1 vs 20.1 wks) and OR (59.2% vs 22.5%) in pts treated with len/dex compared to dex-placebo (p <0.001). Although subgroup analysis of pts with prior thal therapy revealed that pts who received len/dex had significantly improved OR, PR CR and median TTP than pts who received dex-placebo, OR, CR and TTP were highest in len/dex pts not previously treated with thal. Multivariate analysis indicates that after controlling for the treatment factor and baseline disease characteristics, whether or not pt had prior exposure to thal is a marginally significant variable to predict TTP. The risk of deep venous thrombosis and pulmonary embolism in these subgroups will be updated on further analysis. Conclusions: Lenalidomide in combination with dexamethasone is more effective than dexamethasone-placebo regardless of prior thalidomide in relapsed/refractory multiple myeloma. [Table: see text] [Table: see text]

Relapsed/Refractory Multiple Myeloma Patients Treated with Lenalidomide/Dexamethasone Who Achieve a Complete or near Complete Response Have Longer Overall Survival and Time to Progression Compared with Patients Achieving a Partial Response.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 3598-3598 ◽  
Author(s):  
Jean-Luc Harousseau ◽  
Donna Weber ◽  
Meletios Dimopoulos ◽  
Marta Olesnyckyj ◽  
Zhinuan Yu ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Overall Survival ◽  
Partial Response ◽  
Adverse Events ◽  
Complete Response ◽  
Response To Therapy ◽  
Phase Iii ◽  
Time To Progression ◽  
Refractory Multiple Myeloma ◽  
Duration Of Response

Abstract Background: There is ongoing debate about what would be considered an acceptable response to therapy in patients with relapsed/refractory multiple myeloma (MM). Lenalidomide (Len) is an immunomodulatory compound. Two recent phase III randomised trials (MM-009 and MM-010) showed Len in combination with Dexamethasone (Dex) provided significantly better overall response (OR), complete response (CR), overall survival (OS) and time to progression (TTP) compared with Dex alone in patients with relapsed/refractory MM. Approximately 60% of patients achieved an OR (61% in MM-009 and 60% in MM-010), including a CR in 15% (14% and 16%, respectively), Median OS was ≥29.5 months (29.5 and not yet reached) and median TTP was ≥11.1 months (11.1 months and 11.3 months, respectively). Here, we compare outcomes in patients with a CR or near CR (nCR) vs those with a partial response (PR). Methods: Data for patients who received Len/Dex in the MM-009 or MM-010 studies were pooled for this analysis. Patients received Len (25 mg/day on days 1–21 of every 28-day cycle) and Dex 40mg PO q.d. on days 1–4, 9–12, and 17–20 (for the first four cycles). After 4 cycles, Dex 40 mg/day was administered only on days 1–4. Response to therapy, TTP, OS, duration of response, and time to response, as well as adverse events were assessed. Response rate and TTP are based on data obtained before unblinding (June 2005 [MM-009] and August 2005 [MM-010]). Results: Of 353 patients treated with Len/Dex, 214 (61%) had PR or better (86 with CR/nCR; 128 with PR). Baseline characteristics were comparable between patient groups; most patients had stage III disease (63% vs 66%) and an Eastern Cooperative Oncology Group (ECOG) score of 0–1 (83% vs 90%). More patients with CR/nCR had received ≥2 prior antimyeloma regimens/stem cell transplant than patients with PR (88% vs 70%). Patients with CR/nCR had significantly longer median TTP and OS compared with those with PR (Table). The median duration of response was significantly higher among patients with CR/nCR (not yet reached vs 38 weeks; p&lt;0.001). Fewer patients with CR/nCR relapsed compared with those with PR (38% vs 43%). The times to CR/nCR and PR were comparable. The most common grade 3–4 adverse events were neutropenia (43% vs 41%), thrombocytopenia (13% vs 16%), anaemia (12% vs 9%) and pneumonia (12% vs 6%). Rates of febrile neutropenia were low (1% vs 3%). Conclusion: Len/Dex treatment is associated with longer OS and TTP in patients with relapsed/refractory MM who achieve a CR than in patients who achieve a PR. Len/Dex CR/nCR (n=86) PR (n=128) P value Median OS (weeks) &gt;132.7 &gt;118.1 &lt;0.01 Median TTP (weeks) &gt;65.1 46.0 &lt;0.001 (n=84) (n=126) Duration of response (weeks) NE 38 &lt;0.001 Time to response (weeks) 10.2 10.9 NE = not yet evaluable

The Prolonged Time to Progression with Pegylated Liposomal Doxorubicin + Bortezomib Versus Bortezomib Alone in Relapsed or Refractory Multiple Myeloma Is Unaffected by Extent of Prior Therapy or Previous Anthracycline Exposure.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 410-410 ◽  
Author(s):  
Joan Blade ◽  
Jesus San Miguel ◽  
Arnon Nagler ◽  
Pieter Sonneveld ◽  
Andrew Spencer ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Combination Therapy ◽  
Liposomal Doxorubicin ◽  
Pegylated Liposomal Doxorubicin ◽  
Phase Iii ◽  
Time To Progression ◽  
Total Study Population ◽  
Refractory Multiple Myeloma ◽  
Prior Therapy ◽  
Heterogeneity Test

Abstract Recently, a significant improvement in time to progression (TTP) was reported for pegylated liposomal doxorubicin (PLD) + bortezomib combination therapy vs. bortezomib monotherapy in a phase III randomized trial in relapsed or refractory multiple myeloma (RRMM) (Orlowski, JCO 2007). This pre-specified analysis assessed the efficacy of PLD+bortezomib in RRMM based on the number of prior lines of therapy and previous anthracycline exposure status. Patients with ≥1 prior therapy were randomized to receive PLD at 30 mg/m2 on day 4 and bortezomib at 1.3 mg/m2 on days 1, 4, 8, and 11, or bortezomib alone for up to eight 21-day cycles, or at least 2 cycles beyond CR, or optimal response unless disease progression, or unacceptable toxicities occurred. The baseline beta-2 microglobulin levels were comparable between the subgroup with ≥2 prior treatments and that with 1 treatment (median 3.98 vs. 4.01 mg/L), as well as between anthracycline-exposed and -naïve patients (median 3.91 vs. 4.55 mg/L). The improved TTP reported previously with PLD+bortezomib over bortezomib in the total study population was similarly observed in all four subgroups of patients (patients with ≥2 lines of prior therapy or 1 prior therapy, anthracycline-exposed (median 144 mg/m2 in both treatment arms) or -naïve groups (Table)), indicating a consistent therapeutic benefit favoring the PLD+bortezomib combination. Furthermore, TTP was comparable for the PLD+bortezomib combination between groups with ≥2 lines of prior therapy vs. 1 prior therapy (heterogeneity test, p=0.523), as well as patients who were anthracycline-exposed or -naïve (heterogeneity test, p=0.716). Incidence of treatment-related SAEs, grade 3/4 neuropathy, and symptomatic cardiac events was comparable between treatment arms in each subgroup (Table). PLD-related hand-foot syndrome was also <10% in all PLD+bortezomib subgroups. These results demonstrate that PLD+bortezomib combination therapy significantly improves TTP compared to bortezomib alone, regardless of the number of prior lines of therapy, or anthracycline exposure.

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