Long-Term Outcomes of Autologous Transplantation in Multiple Myeloma: Significant Survival Benefit of Novel Drugs in Post-Transplantation Relapse

BackgroundAutologous stem cell transplantation (autoSCT) has an important role in the treatment of patients with symptomatic multiple myeloma (MM). Treatment options for myeloma have expanded in the past decade, and it seems that patients who are treated with novel drugs such as thalidomide and bortezomib for relapse after autoSCT have longer overall survival (OS).Patients and MethodsHerein, we describe the long-term outcome of a cohort of 185 patients with newly diagnosed MM treated with autoSCT. We have analyzed factors that might predict for long-term survival.ResultsFollowing autoSCT, the overall response rate was 94% (173 of 185 patients); 29% (53 of 185 patients) were in complete remission (CR). Median time to progression (TTP) and OS from start of therapy were 39.8 months and 77.9 months, respectively. The median follow-up was 103.8 months (range, 60.8-144.8 months); 23% of the patients are alive and disease free, 21% of the patients are alive with relapse, and 56% of the patients have died. On multivariate analysis, factors associated with significantly better OS were International Staging System (ISS) disease stage < III (hazard ratio [HR], 2.6; P < .001), achievement of CR after autoSCT (HR, 2.8; P < .001) and use of thalidomide (HR, 4.3; P < .001) and/or bortezomib (HR, 7.3; P < .001) in posttransplantation relapse treatment. The patients' age, renal impairment, disease status before autoSCT and maintenance therapy with interferon-α (IFN-α) or IFN-α and dexamethasone did not significantly affect TTP and OS after transplantation.ConclusionAccording to our results, the achievement of CR after transplantation, ISS stage other than III, and administration of thalidomide or bortezomib in posttransplantation relapse were significant parameters favoring long-term posttransplantation survival.     

Analysis of the Efficacy of Thalidomide Plus Dexamethasone-Based Regimens in Patients With Relapsed/Refractory Multiple Myeloma Who Received Prior Chemotherapy,Including Bortezomib and Lenalidomide: KMM-166 Study

BackgroundFor patients with multiple myeloma (MM) that relapsed after treatment with bortezomib- and lenalidomide-based regimens, there were no other treatment options in Korea until 2016. We aimed to determine the efficacy of thalidomide plus dexamethasone-based regimens in patients with relapsed/refractory MM (RRMM).Patients and MethodsWe conducted a multicenter retrospective analysis in Korea for patients with RRMM treated with thalidomide-based regimens who previously received bortezomib and immunomodulatory agents (IMiDs), including thalidomide and lenalidomide.ResultsIn 47 patients with RRMM, the median age was 64 years and the median number of previous treatment lines, including bortezomib and IMiDs, was 3. Primary resistance to bortezomib and lenalidomide was observed in 12 (26%) and 8 (17%) patients, respectively. The most common regimen was a combination of thalidomide, cyclophosphamide, and dexamethasone. The overall response rate was 38%; 2 patients (4%) experienced a complete response, and 2 patients (4%) experienced a very good partial response. The overall response rate of patients previously exposed to thalidomide was 53%. The median progression-free survival was 5.9 months, and overall survival was 9.2 months. Patients with disease that responded to the thalidomide-based regimen had better progression-free survival compared to those who did not (median, 8.8 vs. 2.5 months; P = .008). The most common adverse events were anemia (51%) for hematologic toxicities and peripheral neuropathy (30%) for nonhematologic toxicities.ConclusionThalidomide-based regimens are potential salvage treatment options for patients with RRMM, even those with disease with prior resistance to IMiDs.     

Bortezomib in patients with relapsed or refractory mantle cell lymphoma: updated time-to-event analyses of the multicenter phase 2 PINNACLE study

Background: We previously reported results of the phase 2, multicenterPINNACLE study, which confirmed the substantial single-agentactivity of bortezomib in patients with relapsed or refractorymantle cell lymphoma (MCL). Materials and methods: We report updated time-to-event data,in all patients and by response to treatment, after extendedfollow-up (median 26.4 months). Results: Median time to progression (TTP) was 6.7 months. Mediantime to next therapy (TTNT) was 7.4 months. Median overall survival(OS) was 23.5 months. In responding patients, median TTP was12.4 months, median duration of response (DOR) was 9.2 months,median TTNT was 14.3 months, and median OS was 35.4 months.Patients achieving complete response had heterogeneous diseasecharacteristics; among these patients, median TTP and DOR werenot reached, and median OS was 36.0 months. One-year survivalrate was 69% overall and 91% in responding patients. MedianOS from diagnosis was 61.1 months, after median follow-up of63.7 months. Activity was seen in patients with refractory diseaseand patients relapsing following high-intensity treatment. Toxicitywas generally manageable. Conclusions: Single-agent bortezomib is associated with lengthyresponses and notable survival in patients with relapsed orrefractory MCL, with considerable TTP and TTNT in respondingpatients, suggesting substantial clinical benefit. Key words: bortezomib, mantle cell lymphoma, refractory, relapsed, response, survival Received for publication May 1, 2008. Revision received August 27, 2008. Accepted for publication September 3, 2008.     

Features and risk factors of peripheral neuropathy during treatment with bortezomib for advanced multiple myeloma

BackgroundBortezomib is a first-in-class proteasome inhibitor with remarkable antitumor activity that is approved for the treatment of patients with multiple myeloma. Peripheral neuropathy (PN) is a frequent adverse event reported with bortezomib use.Patients and MethodsThe aim of this retrospective, single-center study was to determine the characteristics of bortezomib-associated PN in 100 patients with advanced myeloma. Peripheral neuropathy was evaluated by investigator's assessment.ResultsWith a median follow-up of 8 months (range, 0.1–32 months) from bortezomib initiation, bortezomib-associated PN was observed in 38 patients (38%; 95% CI, 28%–47%), with grade 3 and 4 PN occurring in 5 patients and 1 patient, respectively. Median time to onset of bortezomib-associated PN was 53 days (range, 11–182 days). Of the 38 patients with bortezomib-associated PN, resolution or improvement occurred in 20 patients (53%) at a median of 3 months (range, 1–8 months). In multivariate analysis, the total number of cycles of bortezomib (< 4 cycles or > 4 cycles; P = .03; odds ratio [OR], 2.6; 95% CI, 1.1–6.1) and a previous history of thalidomide therapy (P = .02; OR, 3.9; 95% CI, 1.2–12.6) were significantly associated with an increased incidence of bortezomib-associated PN.ConclusionWe conclude that, though relatively frequent, bortezomib-associated PN is reversible in a majority of patients. However, bortezomib-associated PN seems to be dependent on previous therapy with thalidomide, suggesting that bortezomib followed by thalidomide could be an optimal sequence of administration of these drugs in the salvage setting.     

Analysis of Efficacy and Prognostic Factors of Lenalidomide Treatment as Part of a Dutch Compassionate Use Program

Background and Methods:To obtain efficacy and safety data on lenalidomide treatment outside of clinical trials, we analyzed the clinical data of 114 patients with refractory or relapsed multiple myeloma treated with lenalidomide on a compassionate use basis. The recommended treatment consisted of lenalidomide 25 mg given on days 1-21 of a 28-day cycle, in combination with dexamethasone. A median of 3 previous lines of therapy were given, including thalidomide in 91%. Most patients were treated until progression or intolerable toxicity.Results:The median number of cycles was 7 (range, 1-21+ cycles) with a maximum response after a median of 3 cycles (range, 1-10 cycles). The overall response rate was 69%, including complete response in 6%, very good partial response in 19%, and partial response in 44%. The response rate was not influenced by previous thalidomide and/or bortezomib treatment. The median time to progression (TTP) was 9 months and the median overall survival (OS) was 22 months. A significantly longer TTP was observed in patients who previously underwent allogeneic stem cell transplantation (12.5 months vs. 8 months; P = .036). Overall survival was significantly affected by performance status (P < .0001). Lenalidomide toxicity was predominantly hematologic (37%; Common Toxicity Criteria ≥ 3) and the incidence of venous thrombotic events was low (5%) using the recommended prophylaxis.Conclusion:This analysis confirms that, outside clinical prospective trials, treatment with lenalidomide is highly effective and feasible in heavily pretreated patients with multiple myeloma.     

KD-PACE Salvage Therapy for Aggressive Relapsed Refractory Multiple Myeloma,Plasma Cell Leukemia and Extramedullary Myeloma

BackgroundPatients with advanced/aggressive multiple myeloma have limited treatment options to achieve rapid disease control. In eligible patients, bortezomib, dexamethasone, thalidomide, cisplatin, doxorubicin, cyclophosphamide, and etoposide is often used. However, many patients are refractory to or have toxicities from bortezomib and there is a need for bridging therapy. We have used a modified regimen incorporating the second-generation proteasome inhibitor carfilzomib (carfilzomib, dexamethasone, thalidomide, cisplatin, doxorubicin, cyclophosphamide and etoposide [KD-PACE]) instead of bortezomib for relapsed/refractory multiple myeloma.Patients and MethodsThis 2-center retrospective study included consecutive patients receiving KD-PACE for relapsed or refractory multiple myeloma, plasma cell leukemia, or extramedullary myeloma. The primary outcome was the feasibility of KD-PACE as a bridging therapy to a more definitive treatment option.ResultsFifty-two patients were included. The median age was 57 years, and 67% were male. Thirty-one patients were bridged with KD-PACE to autologous hematopoietic stem cell transplant (29%), allogenic hematopoietic stem cell transplant (27%), or a clinical trial (12%). Patients bridged to autologous hematopoietic stem cell transplant, allogenic hematopoietic stem cell transplant, or a clinical trial had a superior progression-free survival (8.3 months vs 2.3 months in the nonbridged group; P < .001) and overall survival (median, 16.7 months vs 4.3 months in the nonbridged group; P < .001). No unexpected toxicities occurred from the treatment regimen.ConclusionKD-PACE is a promising treatment option for select patients with advanced/aggressive forms of myeloma requiring rapid disease control before a more definitive salvage therapy such as auto/allotransplantation or a clinical trial.     

Adding Cyclophosphamide to Bortezomib and Dexamethasone was not Associated With Improved Outcomes of Patients With Newly Diagnosed Light Chain Amyloidosis: A Retrospective Study

IntroductionBefore 2021, the combination of bortezomib, cyclophosphamide, and dexamethasone (VCd) was one of the most used upfront therapy for systemic immunoglobulin light chain (AL) amyloidosis. Recently, daratumumab in combination with VCd resulted in improved outcomes compared to VCd. However, it's still unclear the role of cyclophosphamide in this combination.Materials and MethodsWe conducted this retrospective single-institutional study to compare the outcomes of upfront bortezomib and dexamethasone with or without cyclophosphamide (VD vs. VCd).ResultsOf 136 total patients, 62 received VD and 74 received VCd. The median age was 64 and the median number of organs involved was 2. Hematologic response was achieved among 73.4% patients in the VD arm and 85.9% in the VCd arm at 3 months (P = .15). Best organ response was not different between 2 arms (34.1% vs. 52.9% for VD and VCd arms, respectively; P = .28). After a median follow-up of 24.4 months, 2-year OS for VD and VCd arm was 70.6% and 84.6% respectively. The median overall survival was 70 months for VD arm and not reached for VCd arm (P = .30). There was no statistically significant difference in median time to next therapy (9.3 vs. 13.5 months for VD and VCd arms, respectively. P = .99).Conclusionthe addition of cyclophosphamide to VD was not associated with improved outcomes of patients with AL amyloidosis in this retrospective study.     

IgD multiple myeloma a descriptive report of 17 cases: survival and response to therapy

Background

Immunoglobulin D multiple myeloma (MM) is rare and has a poorer prognosis than other MM isotypes.

Design and methods

Seventeen patients (pts) diagnosed from 1993 to 2009 with IgD MM were selected from six institutions of Multiple Myeloma Latium-Region GIMEMA Working Group.

Results

Median age was 55 years, 14 patients had bone lesions, eight had renal impairment with estimated glomerular filtration rate (eGFR) < 50 ml/min, one serum calcium ≥ 12 mg/dl, 11 had lambda light chains, five stage III of ISS, six with chromosomal abnormalities. Six pts received conventional chemotherapy (CT): five melphalan + steroids based regimens. Eleven underwent high-doses of chemotherapy with autologous stem cell transplantation (HDT/ASCT), five single and six tandem ASCT: six received bortezomib and/or thalidomide as induction therapy and five VAD. Thalidomide maintenance was used in two pts: one in HDT/ASCT and one in CT group; bortezomib was used in one patient after HDT/ASCT. At a median follow up of 38 (range 19-60) and 50 months (range 17-148) for pts treated with CT and HDT/ASCT, respectively, the overall response rate (ORR) was 83% and 90%. In the group of patients treated with CT, median overall survival (OS) was 34 months (95% CI 15- 54 months), median progression free survival (PFS) was 18 months (95% CI 3-33 months) and median duration of response (DOR) was 7 months (95% CI 5-9 months). Median OS, PFS and DOR were not reached at the time of this analysis in the HDT/ASCT group of patients. Death was observed in 27.3% of pts treated with HDT/ASCT and in 66.7% undergone CT.

Conclusions

Despite the retrospective analysis and the small number of pts our study showed that the use of HDT/ASCT seems to improve also the prognosis of IgD MM patients. Treatment options including new drugs, before and after stem cell transplantation, may further improve the outcomes of these patients.     

Thalidomide maintenance following high-dose melphalan with autologous stem cell support in myeloma

BackgroundRecent experience with thalidomide maintenance after high-dose chemotherapy with autologous stem cell support has demonstrated improvement in progression-free survival (PFS) and overall survival (OS). We further explored the tolerability and efficacy of lower doses of maintenance thalidomide in this single-institution study.Patients and MethodsThirty-eight patients with myeloma were enrolled and treated with melphalan 200 mg/m² followed by autologous stem cell transplantation. Thalidomide 50 mg per day was started on day ≥ 60 after recovery of blood counts and was escalated to a maximum dose of 200 mg per day. Responses were assessed at 2 months, 1 year, and 2 years after transplantation.ResultsOf the 38 enrolled patients, 7 patients never received thalidomide. Among 31 patients receiving thalidomide, complete or very good partial responses were observed in 65% and 42% of patients at 1 and 2 years, respectively. Tolerability was a major issue, with only 17 patients completing 1 year of thalidomide. The goal of dosing 200 mg per day was achieved in just 17 of 31 patients, and the median tolerated thalidomide dose was 100 mg per day. Sensory neuropathy was the primary reason for dose modification and discontinuation. No thromboembolic events were observed. The median PFS was 20.8 months, and the median OS was > 60 months.ConclusionThalidomide maintenance at a goal dose of 200 mg per day was not feasible in this population, with our data suggesting that 100 mg per day is a more reasonable maintenance dose.     

Azacitidine Monotherapy in Patients With Treatment-Naïve Higher-risk Myelodysplastic Syndrome: A Systematic Literature Review and Meta-analysis

BackgroundThe global incidence of myelodysplastic syndromes (MDS) has been estimated as 0.06 to 0.26/100,000. Since their introduction, hypomethylating agents have played a central role in the treatment of MDS, with heterogeneous real-world outcomes.Materials and MethodsWe assessed and synthesized clinical outcomes of azacitidine (AZA) monotherapy in treatment-naïve patients with higher-risk MDS. A systematic literature review was conducted by searching MEDLINE, Embase, and CENTRAL to identify randomized clinical trials (RCTs) and observational studies, both prospective and retrospective, reporting complete remission (CR), partial remission (PR), overall survival (OS), duration of response (DOR), time-to-response (TTR), and myelosuppressive adverse events (AEs) for patients treated with AZA monotherapy. Noncomparative meta-analyses were used to summarize effects.ResultsThe search identified 3250 abstracts, of which 34 publications describing 16 studies (5 RCTs, 3 prospective, and 8 retrospective observational) were included. Across all studies, pooled CR was 16%; PR was 6%; Median OS was 16.4 months; median DOR was 10.1 months; median TTR was 4.6 months. Proportions of grade 3/4 anemia and thrombocytopenia AEs were 10% and 30%.ConclusionsThe effectiveness and efficacy of AZA monotherapy—as measured by CR and median OS—was limited. These findings highlight a significant unmet medical need for effective treatments for patients with higher-risk MDS.     

A Multicenter Retrospective Study of Mogamulizumab Efficacy in Adult T-Cell Leukemia/Lymphoma

BackgroundMogamulizumab, a defucosylated humanized monoclonal antibody targeting C-C chemokine receptor 4, recently became available for the treatment of adult T-cell leukemia/lymphoma (ATL). We conducted a multicenter retrospective study of the efficacy of mogamulizumab in ATL treatment in patients on Hokkaido Island, Japan.Materials and MethodsA total of 125 patients with ATL treated from January 2010 to December 2014 in 20 hospitals affiliated with the Hokkaido Hematology Study Group were enrolled in the present retrospective study.ResultsOf the 125 ATL patients, 62 (46.6%) presented with the acute type, 51 (38.3%) with the lymphoma type, and 12 (9.0%) with the chronic type; the latter group included 7 unfavorable chronic cases. The median age at diagnosis was 68 years (range, 35-86 years). The median survival for those with acute, lymphoma, and unfavorable chronic types was 302, 279, and 921 days, respectively. Advanced age, high lactate dehydrogenase level, poor performance status (3-4), and the existence of B symptoms were unfavorable prognostic factors for overall survival (OS). Survival rate calculated from the day of diagnosis was significantly higher in patients treated with mogamulizumab. The OS of individuals receiving hematopoietic stem cell transplantation (HSCT) was superior to that of the non-HSCT group. The median interval between the last mogamulizumab dose and allogeneic HSCT was 38 days (range, 21-53 days). Of the 22 HSCT recipients who were not treated with mogamulizumab, overall acute graft-versus-host disease (aGVHD) and grade III-IV aGVHD occurred in 12 (54.5%) and 3 (13.6%) patients, respectively. However, overall aGVHD and grade III-IV aGVHD developed in 8 (88.9%) and 3 (33.3%) of the 9 HSCT recipients treated with mogamulizumab, respectively.ConclusionMogamulizumab improves OS in patients with ATL, although its use in HSCT patients might trigger severe GVHD. Determining the optimal pre-HSCT mogamulizumab treatment regimen is thus a priority.     

Outcome and Prognostic Features in Pediatric Acute Megakaryoblastic Leukemia Without Down Syndrome: A Retrospective Study in China

BackgroundAcute megakaryoblastic leukemia (AMKL) is a biologically heterogeneous subtype of acute myeloid leukemia that originates from megakaryocytes. Patients with AMKL with non-Down syndrome (DS) had a poorer prognosis. However, clear prognostic indicators and treatment recommendations for this subgroup remain controversial.Patients and MethodsHerein, we performed a retrospective study on 40 patients (age ≤ 18 years) with non-Down syndrome AMKL at our institution. We assessed the effect of different prognostic factors, such as their cytogenetic abnormalities, early treatment response, and the role of hematopoietic stem cell transplantation (HSCT) as post-remission treatment on the outcomes.ResultsThe complete remission (CR) rate of the patients was 57.9% and 81.1%, respectively, at the end of induction therapy 1 and 2. The overall survival (OS) and event-free survival rates at 2 years were 41% ± 13% and 41% ± 10%, respectively. An analysis of the cytogenetic features showed that patients with +21 or hyperdiploid (> 50 chromosomes) had significantly better OS than those in other cytogenetic subgroups (P_log-rank = .048 and P_log-rank = .040, respectively). Besides cytogenetics, an excellent early treatment response (CR and minimal residual disease < 1% after induction therapy 1) also provided a significant survival benefit in univariate analysis in our study. However, multivariate analysis indicated that allogeneic HSCT was the only independent prognostic marker (relative risk, 11.192; 95% confidence interval, 2.045-61.241; P = .005 for OS and relative risk, 5.400; 95% confidence interval, 1.635-17.832; P = .006 for event-free survival, respectively).ConclusionAMKL in patients with non-Down syndrome has a poor outcome. With poor OS but CR rates comparable with other acute myeloid leukemia subtypes, allogenic HSCT may be a better option for post-remission therapy than conventional chemotherapy, especially for those having a poor response to induction therapy.     

Real-world Outcomes With Cumulative Bortezomib Dose and Efficacy in the Treatment of Transplant-ineligible Multiple Myeloma With Cyclophosphamide,Bortezomib, and Dexamethasone

BackgroundHigher cumulative dose of bortezomib, a key component of Multiple Myeloma (MM) treatment regimens, has been shown to improve outcomes in MM patients, but must be balanced with toxicities including peripheral neuropathy. In this study, we studied the effect of cumulative bortezomib dose on survival, depth of response, and discontinuation rate in transplant ineligible MM patients.Patients and methodsData from 70 patients treated with Cyclophsophamide, Bortezomib, and Dexamethasone (CyBorD) in a single Canadian center were grouped according to above vs below median cumulative bortezomib dose and analyzed for progression-free survival (PFS), overall survival (OS), depth of response, and discontinuation rate.ResultsThere was a trend for lower discontinuation rate (45.7% vs. 68.6%, P = .052) and significantly lower rate of neuropathy-related discontinuation (5.7% vs. 22.9%, P = .035) in patients who received higher than 43.1 mg/m² of bortezomib. The higher-dose group showed a trend for higher rate of complete response (14.3% vs. 5.7%, P = .225) and significantly higher rate of very good partial response or better (77.1% vs. 51.4%, P = .024). There was significantly longer PFS (24.3 vs. 9.1 months, P = .012) and a trend for longer OS (22.4 vs. 61.3 months, P = .061) in the higher-dose group. In landmark analysis after 180 days, PFS (23.5 vs. 24.3 months, P = .941) and OS were similar in both groups.ConclusionHigher cumulative bortezomib dose showed a lower rate of discontinuation, longer survival, and deeper response. Determining risk of treatment intolerance remains important for treatment.     

Immunoglobulin D multiple myeloma: response to therapy,survival, and prognostic factors in 75 patients

BackgroundTo analyze the clinical features, outcomes including efficacy of treatment, and prognostic factors of patients with immunoglobulin D multiple myeloma (IgD MM).Design and methodsSeventy-five patients diagnosed with IgD MM were selected from the Korean Myeloma Registry database (www.myeloma.or.kr).ResultsMedian age was 57 years and the main presenting features were bone pain (77%). Renal function impairment and hypercalcemia were present in 40 (53%) and 20 (27%) patients. Sixty-seven patients (89%) had lambda light chains. Forty-eight patients (64%) were of stage III by International Staging System. Twenty-six patients (53%) had chromosomal abnormalities mostly by conventional cytogenetics. Thirty-nine patients (54%) were treated with vincristine, adriamycin, and dexamethasone chemotherapy; the overall response rate (ORR) of 56%. Sixteen patients (22%) received first-line chemotherapy including new drugs (bortezomib or thalidomide), with an ORR of 81%. At a median follow-up time of 28.6 months, median overall survival (OS) was 18.5 months. Age, extramedullary plasmacytoma, del(13) or hypoploidy, serum β₂ microglobulin level, and platelet count were significant prognostic factors for OS.ConclusionsIgD MM is an aggressive disease that is usually detected at an advanced stage. Despite a positive initial response, survival after relapse was dismal. Intensive treatment strategies before and following stem cell transplantation may improve outcomes in younger patients.     

Frontline chemotherapy with bortezomib-containing combinations improves response rate and survival in primary plasma cell leukemia: a retrospective study from GIMEMA Multiple Myeloma Working Party

BackgroundThe best therapeutic approach for primary plasma cell leukemia (PPCL) remains unknown so far. In very limited studies, the poor clinical outcome of this aggressive variant of multiple myeloma seemed to be ameliorated by the use of the proteasome inhibitor bortezomib. Aiming to provide more consolidated data, this multicenter retrospective survey focused on unselected and previously untreated PPCL patients who had received bortezomib as frontline therapy.Patients and methodsTwenty-nine patients with PPCL were collected. Bortezomib was given at standard doses and schedules, in various combinations with dexamethasone, thalidomide, doxorubicin, melphalan, prednisone, vincristine, and cyclophosphamide.ResultsAn overall response rate of 79% was observed, with 38% of at least very good partial remission. Grade 3–4 hematological, neurological, infectious, and renal toxic effects occurred in 20%, 21%, 16%, and 4% of patients, respectively. After a median follow-up of 24 months, 16 patients were alive (55%), 12 of whom were in remission phase and 4 relapsed. The best long-term results were achieved in patients who received stem-cell transplantation after bortezomib induction.ConclusionBortezomib, used as initial therapy, is able to increase the percentage and the quality of responses in PPCL patients, producing a significant improvement of survival.     

Serum C-reactive protein at diagnosis and response to therapy is the most powerful factor predicting outcome of multiple myeloma treated with thalidomide/ anthracycline-based therapy

BackgroundFew studies have focused on factors affecting outcome in patients with multiple myeloma (MM) treated with thalidomide-based therapy. We investigated factors affecting response, progression-free survival (PFS), and overall survival (OS) in patients with MM treated with the thalidomide, dexamethasone, and pegylated liposomal doxorubicin (ThaDD) regimen with the aim to select patients benefiting more from this therapy.Patients and MethodsSixty-six patients with MM were treated first line with the ThaDD regimen. We analyzed demographics and disease-related characteristics to search for factors affecting response (≥ very good partial remission [VGPR] vs. < VGPR], PFS, and OS.ResultsOverall, 45 patients (68%) showed response ≥ VGPR; median TTP and OS were 23.5 months and 35.5 months, respectively. Multivariate analysis selected only serum C-reactive protein (sCRP) as a predictive factor for response (P < .0001). By multivariate analysis, normal sCRP level (P = .001) and response to treatment ≥ VGPR (P = .007) were found to be associated with longer PFS. The factors that remained significantly associated with a longer OS when assessed by multivariate analysis were normal sCRP level (P = .005) and response to therapy ≥ VGPR (P = .019).ConclusionSerum C-reactive protein before therapy and response after therapy are the only factors useful in identifying patients benefiting from anthracycline/thalidomide—based therapy.     

A randomised,double-blind,placebo-controlled trial of trametinib,an oral MEK inhibitor,in combination with gemcitabine for patients with untreated metastatic adenocarcinoma of the pancreas

BackgroundTrametinib, an oral mitogen/extracellular signal-related kinase (MEK)1/2 inhibitor, holds promise for malignancies with rat sarcoma (RAS) mutations, like pancreas cancer. This phase II study was designed to determine overall survival (OS) in patients with pancreas cancer treated with trametinib and gemcitabine. Secondary end-points included progression-free survival (PFS), overall response rate (ORR) and duration of response (DOR); safety end-points were also assessed.MethodsAdults with untreated metastatic adenocarcinoma of the pancreas were randomised (1:1) to receive intravenous gemcitabine 1000 mg/m² (weekly × 7 for 8 weeks, then days 1, 8 and 15 of 28-day cycles) plus trametinib or placebo 2 mg daily. RAS mutations were determined in circulating free DNA (cfDNA) and archival tumour tissue. OS was evaluated in kirsten rat sarcoma viral oncogene homolog (KRAS) mutant and wild-type subgroups.ResultsBaseline characteristics for 160 patients were similar in both treatment arms. There was no significant difference in OS (hazard ratio (HR) 0.98; 95% confidence interval (CI), 0.67–1.44; P = .453); median OS was 8.4 months with gemcitabine plus trametinib and 6.7 months with gemcitabine plus placebo. Median PFS (16 versus 15 weeks), ORR (22% versus 18%) and median DOR (23.9 versus 16.1 weeks) were also similar for trametinib and placebo arms, respectively. KRAS mutation-positive patients (n = 103) showed no difference in OS between arms. Thrombocytopenia, diarrhoea, rash and stomatitis were more frequent with trametinib, as was grade 3 anaemia.ConclusionsThe addition of trametinib to gemcitabine did not improve OS, PFS, ORR or DOR in patients with previously untreated metastatic pancreas cancer. Outcomes were independent of KRAS mutations determined by cfDNA.     

Day +100 Platelet Count Predicts Survival After Allogeneic Hematopoietic Stem-Cell Transplantation in Children With Hematologic Malignancies

IntroductionRecovery of platelet count by day 100 after hematopoietic stem-cell transplantation (HSCT) is affected by many factors and has been reported to be a predictor of overall survival (OS) in a variety of diseases and donor types. We investigated the correlation between day +100 platelet count and OS after allogeneic HSCT in a relatively homogeneous cohort of pediatric patients with hematologic malignancies.Patients and MethodsWe conducted a retrospective study of 152 consecutive patients who underwent allogeneic HSCT at the Children’s Cancer Hospital Egypt between 2009 and 2015 with a minimum follow-up duration of 1 year after transplantation. All eligible patients received myeloablative conditioning, and all had matched related donors. Patients who survived without relapse until day 100 after HSCT were divided into 2 groups: early platelet recovery (EPR; platelet count ≥ 100 × 10⁹/L at day +100 after transplantation) and delayed platelet recovery (DPR; platelet count < 100 × 10⁹/L at day +100 after transplantation).ResultsAt day +100, 113 patients (74%) had EPR and 39 patients (26%) had DPR. With a median follow-up of 41 months (range, 12-93 months), 41 patients (27.2%) died, 35 of relapsed disease. The 3-year disease-free survival (DFS) and OS were 68 ± 7.84% and 71.9 ± 7.84%, respectively. The 3-year OS was 77.9% in the EPR group and 57.1% in the DPR group (P = .006). Three-year DFS of the EPR and DPR groups were 73.2 ± 9% and 54.8 ± 16.3%, respectively (P = .02). Incidence of disease relapse for EPR and DPR patients was 22.6% and 39.5%, respectively (P = .04). Multivariate analysis for survival identified DPR as a predictor of decreased survival (P = .002).ConclusionPatients with a robust platelet count at day 100 are likely to do well. However, patients who do not experience a platelet count of ≥ 100 × 10⁹/L have inferior long-term OS and DFS and may require further evaluation at the day 100 time point.     

Clinical outcomes of patients with plasma cell leukemia in the era of novel therapies and hematopoietic stem cell transplantation strategies: a single-institution experience

BackgroundPCL carries a poor prognosis and the optimal management remains unknown.Patients and MethodsTo evaluate the outcome of patients with PCL in the era of novel agents and innovative transplantation strategies, we conducted a review of patients with PCL who were treated at our institution from August 2003 to October 2009. Our primary endpoint was to determine overall survival, which was calculated from time of PCL diagnosis to death or last follow-up. Secondary endpoints included response rates and analyses regarding how the novel agents and presence of adverse cytogenetic analyses affected outcomes.ResultsWe identified 25 patients with PCL (13 with primary PCL [pPCL], 12 with secondary PCL [sPCL]) from our institution. Eighteen patients received bortezomib-based regimens, 19 received high-dose melphalan followed by autologous hematopoietic stem cell transplantation (HCT), and 6 underwent allogeneic HCT. The median overall survival for all patients was 23.6 months. Bortezomib-treated patients had a median survival of 28.4 months vs. 4.0 months for the non-bortezomib–treated group (P < .001).ConclusionsOur analysis suggests that patients with PCL who were treated with bortezomib and/or allogeneic HCT had improved outcomes.