Response adaptive salvage with KTd and ASCT for functional high-risk multiple myeloma—The Australasian Leukemia and Lymphoma Group (ALLG) MM17 Trial

We evaluated re-induction incorporating carfilzomib–thalidomide–dexamethasone (KTd) and autologous stem cell transplantation (ASCT) for newly diagnosed multiple myeloma (NDMM) refractory, or demonstrating a suboptimal response, to non-IMID bortezomib-based induction. KTd salvage consisted of thalidomide 100 mg daily and dexamethasone 20 mg orally combined with carfilzomib 56 mg/m² days 1, 2, 8, 9, 15 and 16, of each 28-day cycle. Following four cycles, patients achieving a stringent complete response proceeded to ASCT whereas those who did not received a further two cycles then ASCT. Consolidation consisted of two cycles of KTd then Td to a total of 12 months post-ASCT therapy. Primary end-point was the overall response rate (ORR) with KTd prior to ASCT. Fifty patients were recruited. The ORR was 78% with EuroFlow MRD negativity of 34% in the intention-to-treat population and 65% in the evaluable population at 12 months post-ASCT. With follow-up >38 months median PFS and OS have not been reached with PFS and OS at 36 months of 64% and 80%, respectively. KTd was well tolerated with grade 3 and grade ≥4 adverse events rates of 32% and 10%, respectively. Response adaptive utilisation of KTd with ASCT is associated with both high-quality responses and durable disease control in functional high-risk NDMM.     

Autologous stem cell transplantation in first remission is associated with better progression-free survival in multiple myeloma

Autologous stem cell transplant (ASCT) is standard consolidation therapy in management of multiple myeloma (MM) patients. We reviewed records of all consecutive MM patients who underwent ASCT with high-dose melphalan at our center from year 2002 to 2016. A total of 141 ASCT were conducted (90 males and 51 females) with median age of 55 years (23–68 years). Median time from diagnosis to transplant was 7 months (3–79), with majority of patients underwent transplant in first remission, while 17 (12%) patients received transplant beyond first remission. Eighty-three percent patients obtained CR/VGPR post-ASCT. Transplant-related mortality was 2.1%. At a median follow up of 54 months, mean overall survival (OS) and progression-free survival (PFS) group were 128.3 months (95% C.I. 111.9–144.7 months) and 73.8 months (95% C.I. 57.7–89.9 months), respectively. On univariate analysis, OS was adversely affected by renal insufficiency (p?=?0.024), while OS was better with CR/VGPR post-ASCT (p?<?0.001) and lenalidomide maintenance therapy (p?=?0.009). PFS was affected by CR/VGPR pre-ASCT (p?=?0.021), CR/VGPR post-ASCT (p?<?0.001), and transplant in first remission (p?=?0.034). On multivariate analysis, lenalidomide maintenance (versus thalidomide) (p?=?0.007) and CR/VGPR response post-ASCT (p?=?0.0003) were found to be predictors for better OS and CR/VGPR response at transplant for better PFS (p?=?0.038). Transplant in first remission versus beyond first remission showed a trend for better PFS (p?=?0.073). Conclusion: Majority of patients obtained CR/VGPR post-ASCT. Longer PFS was seen with patients who were transplanted in first remission.     

Autologous stem cell transplantation in multiple myeloma: improved survival in nonsecretory multiple myeloma but lack of influence of age,status at transplant,previous treatment and conditioning regimen. A single-centre experience in 127 patients

High-dose therapy with autologous stem cell transplantation (ASCT) has become the treatment of choice for symptomatic eligible patients with multiple myeloma (MM). We report our centre experience and analyse retrospectively the prognostic influence of pretransplant characteristics and transplant modalities on response and survival. A total of 127 MM patients (median age: 55.2 years) were transplanted between 1994 and 2001. In all, 69 patients had IgG, 28 IgA, 23 light chain, one IgD and six non secretory MM. At the time of autograft, 6% of patients were in complete remission (CR), 73% in partial remission (PR), 12% showed minor response to previous treatment and 9% had stable or refractory disease. Prior to autograft, 79% of cases had received only one line of chemotherapy and 21% two or more lines. All patients received PBSC support after conditioning with 200 mg/m(2) melphalan alone (100 patients) or melphalan and TBI (27 patients). We evaluated the influence of age (using as cutoff value the ages of 55, 60 and 65 years), type of MM, status pre- and post-ASCT, number of lines of previous regimens, time of ASCT from diagnosis, year of autograft, dose of reinfused CD34+ cells, plasma cell infiltration and beta(2)-microglobulin at diagnosis on overall (OS) and progression-free survivals (PFS) to define patients with better prognosis. Following ASCT, 15% of patients were in CR and 81% in PR, while only two patients progressed. Median OS and PFS from transplantation were 50.4 and 23.5 months, respectively. Median OS from diagnosis was 79.7 months. Transplant-related mortality was 2.3%. Low levels of beta(2)-microglobulin and the achievement of CR post-transplant correlated with longer PFS (P<0.03 and P<0.01, respectively). The median PFS was 36.1, 23.9, 21.1 and 16.4 months for nonsecretory, IgG, IgA and light chain subtypes, respectively. Age was not an important prognostic factor at a cutoff value of 55 or 60 years. We conclude that ASCT is a safe and effective procedure even in resistant cases. The outcome was independent of age, time from diagnosis, previous treatment and conditioning regimen, but there was a tendency for better survival in the nonsecretory patients.     

Role of high-dose melphalan with autologous stem cell transplantation in multiple myeloma patients receiving botezomib-containing induction therapy

To examine the role of high-dose melphalan therapy with autologous stem cell transplantation (HDM/ASCT) in the final outcomes of multiple myeloma (MM) patients receiving bortezomib-containing induction therapy (IT), we analyzed relationships between quality of response after IT including bortezomib or HDM/ASCT and survival. In total, 92 MM patients who received IT with bortezomib followed by HDM/ASCT were enrolled. The median follow-up was 28.0 months. Three-year progression-free survival (PFS) and overall survival (OS) were 41.1 and 72.0 %, respectively. A complete response (CR) after HDM/ASCT was a strong prognostic factor for PFS and OS (p = 0.002 and 0.001, respectively). Additionally, out of 67 patients who failed to achieve CR after IT, 36 (53.7 %) patients achieved CR after HDM/ASCT. PFS and OS in patients with CR after additional HDM/ASCT were similar to those in patients who had already achieved CR after IT. However, achievement of at least very good partial response following IT with bortezomib failed to improve PFS and OS (p = 0.35 and 0.11, respectively). Thus, we conclude that post-HDM/ASCT CR is the best prognostic factor for both PFS and OS regardless of response to bortezomib. Therefore, HDM/ASCT remains an important therapy in MM patients even after introduction of bortezomib IT.     

Post-autologous stem cell transplantation administration of rituximab improves the outcome of patients with aggressive B cell non-Hodgkin’s lymphoma

The major cause of treatment failure following high-dose therapy with autologous stem cell transplantation (ASCT) for aggressive B cell non-Hodgkin’s lymphoma (NHL) is persistent disease or recurrence. We describe our experience with the administration of rituximab post-ASCT, either as maintenance therapy or for the treatment of relapsed disease in patients with aggressive B cell NHL. Fifty-six patients achieved complete remission post-transplant, and 19 of them received maintenance with rituximab. Maintenance with rituximab resulted in statistically significant superior outcome in terms of progression free (PFS; p = 0.002) and overall survival (OS; p = 0.011). The median PFS and OS of patients in the maintenance arm has not been reached yet, while the median PFS and OS of patients in the control arm were 29 and 42 months, respectively. Fifty-four patients had disease progression or relapsed post-ASCT, and 15 of them received rituximab in combination with chemo- and/or radiotherapy in order to achieve disease remission. Therapeutic administration of rituximab resulted in statistically significant prolongation of OS (p = 0.021). The median OS of patients treated with rituximab was 17 months, while median OS of patients in the control group was 10 months. We consider that the results of our study are promising but need to be verified within large randomized trials.     

Lenalidomide, cyclophosphamide and dexamethasone (CRd) for newly diagnosed multiple myeloma: results from a phase 2 trial

The combination of lenalidomide and low-dose dexamethasone is an effective treatment for multiple myeloma (MM). Addition of alkylating agents to lenalidomide or thalidomide results in increased response rates and deeper responses. We designed this trial to study the combination of cyclophosphamide, lenalidomide, and dexamethasone (CRd) as initial therapy for MM. Fifty-three patients with previously untreated symptomatic MM was enrolled. Patients received 4-week treatment cycles consisting of lenalidomide (25 mg daily for 3 weeks), dexamethasone (40 mg weekly), and cyclophosphamide (300 mg/m(2) weekly for 3 weeks). A partial response or better was seen in 85% of patients including 47% with a very good partial response or better. The toxicities were manageable with over 80% of planned doses delivered; six patients went off study for toxicity. The median progression free survival (PFS) for the entire group was 28 months (95% CI: 22.7-32.6) and the overall survival (OS) at 2 years was 87% (95% CI: 78-96). Importantly, 14 patients with high-risk MM had similar PFS and OS as the standard-risk patients (n = 39). CRd is an effective and well-tolerated regimen for upfront therapy of MM with high response rates and excellent 2-year OS, and is suitable for long-term therapy.     

Multiparameter flow cytometric remission is the most relevant prognostic factor for multiple myeloma patients who undergo autologous stem cell transplantation

Minimal residual disease (MRD) assessment is standard in many hematologic malignancies but is considered investigational in multiple myeloma (MM). We report a prospective analysis of the prognostic importance of MRD detection by multiparameter flow cytometry (MFC) in 295 newly diagnosed MM patients uniformly treated in the GEM2000 protocol VBMCP/VBAD induction plus autologous stem cell transplantation [ASCT]). MRD status by MFC was determined at day 100 after ASCT. Progression-free survival (PFS; median 71 vs 37 months, P < .001) and overall survival (OS; median not reached vs 89 months, P = .002) were longer in patients who were MRD negative versus MRD positive at day 100 after ASCT. Similar prognostic differentiation was seen in 147 patients who achieved immunofixation-negative complete response after ASCT. Moreover, MRD(-) immunofixation-negative (IFx(-)) patients and MRD(-) IFx(+) patients had significantly longer PFS than MRD(+) IFx(-) patients. Multivariate analysis identified MRD status by MFC at day 100 after ASCT as the most important independent prognostic factor for PFS (HR = 3.64, P = .002) and OS (HR = 2.02, P = .02). Our findings demonstrate the clinical importance of MRD evaluation by MFC, and illustrate the need for further refinement of MM re-sponse criteria. This trial is registered at http://clinicaltrials.gov under identifier NCT00560053.     

Consolidation therapy with the combination of bortezomib and lenalidomide (VR) without dexamethasone in multiple myeloma patients after transplant: Effects on survival and bone outcomes in the absence of bisphosphonates

Optimizing consolidation treatment in transplant-eligible newly diagnosed multiple myeloma patients in order to improve efficacy and bone-related outcomes is intriguing. We conducted an open-label, prospective study evaluating the efficacy and safety of bortezomib and lenalidomide (VR) consolidation after ASCT, in the absence of dexamethasone and bisphosphonates. Fifty-nine patients, who received bortezomib-based induction, were given 4 cycles of VR starting on day 100 post-ASCT. After ASCT, 58% of patients improved their response status, while following VR consolidation 39% further deepened their response; stringent complete response rates increased to 51% after VR from 24% post-ASCT. VR consolidation resulted in a significant reduction of soluble receptor activator of nuclear factor-κB ligand/osteoprotegerin ratio and sclerostin circulating levels, which was more pronounced among patients achieving very good partial response or better. After a median follow-up of 62 months, no skeletal-related events (SREs) were observed, despite the lack of bisphosphonates administration. The median TTP after ASCT was 37 months, while median overall survival (OS) has not been reached yet; the probability of 4- and 5-year OS was 81% and 64%, respectively. In conclusion, VR consolidation is an effective, dexamethasone- and bisphosphonate-free approach, which offers long OS with improvements on bone metabolism and no SREs.     

Long-term results of thalidomide and dexamethasone (thal–dex) as therapy of first relapse in multiple myeloma

Thal-dex (TD) is an effective therapy for advanced MM. We evaluated TD as salvage treatment of MM patients at first relapse. Thal was given at a daily dose of 100 or 200?mg until progression. Dex was administered 160?mg/month. One hundred patients were enrolled. First line therapy included ASCT (72%) and conventional CHT (28%). Fifty-nine percent received a fixed thal dose of 100?mg/day. The most frequent adverse events were constipation (42%), peripheral neuropathy (58%, 5% grade 3), bradycardia (20%), skin rash (11%), and VTE (7%). Discontinuation of thal due to adverse events was recorded in eight patients. On ITT, 46% of patients achieved at least a PR. Median DOR was 28?months, median time to next therapy was 15.5?months. Median OS, TTP, and PFS were 43, 22, and 21?months, respectively. TTP and PFS were significantly longer for patients with at least PR to TD. TD was an effective salvage treatment for MM patients at first relapse, as demonstrated by durable disease control and prolonged OS. TD was well tolerated, as reflected by the long stay on treatment without disease progression (median 25?months) and a low discontinuation rate due to toxicity (8%).     

D(T)PACE as salvage therapy for aggressive or refractory multiple myeloma

Dexamethasone ± thalidomide with infusion of cisplatin, doxorubicin, cyclophosphamide, and etoposide [D(T)PACE] is generally reserved as salvage therapy for aggressive multiple myeloma (MM) or plasma cell leukaemia (PCL) resistant to conventional therapies. The efficacy and durability of this potentially toxic regimen in this setting is unclear. We identified 75 patients who received D(T)PACE for relapsed/refractory MM at two tertiary care centres: Princess Margaret Hospital, Toronto and Mayo Clinic Arizona. At time of D(T)PACE, 16 patients had PCL and three patients had leptomeningeal disease. Patients were heavily pretreated (median three prior regimens, range 1–12; prior autologous stem cell transplant [ASCT] 33%). Overall response rate was 49% (very‐good partial response 16%, partial response 33%) with stable disease in an additional 36%. Median progression‐free survival (PFS) was 5·5 months (95% confidence interval [CI]:4·3–9·8); overall survival (OS) 14·0 months (95% CI:8·7–19·3). Thirty‐five patients proceeded to ASCT or clinical trial, with median PFS for this subset of 13·4 months (95% CI:7·7–20·1) and OS 20·5 months (95% CI:14·8–63·8). D(T)PACE is an effective salvage therapy for heavily pretreated MM patients. Although the overall response rate of 49% in this poor prognosis cohort is reasonable, the PFS is short, suggesting the best role for D(T)PACE is in bridging to definitive therapy, such as transplantation.     

Early lymphocyte recovery predicts superior survival after autologous hematopoietic stem cell transplantation in multiple myeloma or non-Hodgkin lymphoma

Autologous stem cell transplantation (ASCT) improves survival in patients with previously untreated multiple myeloma (MM) and relapsed, chemotherapy-sensitive, aggressive non-Hodgkin lymphoma (NHL). Lower relapse rates seen in allogeneic stem cell transplantation have been related to early absolute lymphocyte count (ALC) recovery as a manifestation of early graft-verus-tumor effect. In ASCT, the relation between ALC recovery and clinical outcomes in MM and NHL was not previously described. This is a retrospective study of patients with MM and NHL who underwent ASCT at the Mayo Clinic between 1987 and 1999. The ALC threshold was determined at 500 cells/microL on day 15 after ASCT. The study identified 126 patients with MM and 104 patients with NHL. The median overall survival (OS) and progression-free survival (PFS) times for patients with MM were significantly longer in patients with an ALC of 500 cells/microL or more than patients with an ALC of fewer than 500 cells/microL (33 vs 12 months, P <.0001; 16 vs 8 months, P <.0003, respectively). For patients with NHL, the median OS and PFS times were significantly longer in patients with an ALC of 500 cells/microL or more versus those with fewer than 500 cells/microL (not reached vs 6 months, P <.0001; not reached vs 4 months, P <.0001, respectively). Multivariate analysis demonstrated day 15 ALC to be an independent prognostic indicator for OS and PFS rates for both groups of patients. In conclusion, ALC is correlated with clinical outcome and requires further study. (Blood. 2001;98:579-585)     

Prolonged overall survival with second on-demand autologous transplant in multiple myeloma

Between August 1993 and March 2003, 130 consecutive multiple myeloma (MM) patients eligible for high-dose treatment were offered a program including up-front autologous stem cell transplantation (ASCT) after conditioning with 200 mg/m(2) melphalan followed by a second ASCT in case of relapse or progression. A total of 107 (82%) patients completed the first ASCT. The best response obtained after ASCT was complete response (CR) 23%, very good partial response (VGPR) 28%, partial response (PR) 42%, and minimal response (MR) 7%. Median overall survival (OS) and event-free survival (EFS) were 65.4 and 27.7 months, respectively. Relapse or progression occurred in 70 patients; 26 received a second ASCT (with a median time of 20.4 months from first ASCT). A major response (> or =PR) was obtained in 69% of these patients. Median OS and EFS after the second ASCT were 38.1 and 14.8 months. Treatment-related mortality was 1.9% after the first ASCT but no deaths occurred after the second.Our experience suggests that elective up-front single ASCT followed by second ASCT after relapse or progression is a safe and effective global strategy to treat MM patients.     

Phase II study of bortezomib,cyclophosphamide and dexamethasone as induction therapy in multiple myeloma: DSMM XI trial

We assessed the safety and efficacy of bortezomib, cyclophosphamide and dexamethasone (VCD) induction therapy in previously untreated multiple myeloma patients. A total of 414 patients received three 21‐day cycles of VCD prior to autologous stem‐cell transplantation (ASCT). Most common grade ≥3 adverse events were leucopenia (31·4%) and thrombocytopenia (6·8%). The overall response rate (ORR) by investigator‐based assessment was 85·4%. Most patients (74%) underwent successful central laboratory‐based molecular cytogenetic analysis. No clinically relevant differences in ORR post‐induction were seen between patients with or without high‐risk cytogenetic abnormalities (86·2% vs. 84·3%). Further follow‐up data are available for 113 patients receiving ASCT who were included in a prospective consolidation trial (median follow‐up, 55·5 months); median progression‐free survival (PFS) was 35·3 months and median overall survival (OS) was not reached. In patients with high‐risk versus standard‐risk cytogenetics, median PFS was 19·9 vs. 43·6 months (P < 0·0001), and median OS was 54·7 months versus not reached (P = 0·0022). VCD is an effective and tolerable induction regimen; results suggest that VCD induces high response rates independently of cytogenetic risk status, but after long‐term follow‐up, cytogenetic high risk is associated with markedly reduced PFS and OS post‐ASCT.     

Prognostic factors for survival after autologous transplantation: a single centre experience in 133 multiple myeloma patients

Autologous stem cell transplantation (ASCT) has an established role in the treatment of symptomatic multiple myeloma (MM). Our aim was to analyse the impact of selected prognostic parameters on the survival of patients with MM after ASCT. The new International Staging System (ISS) was also evaluated. A total of 133 MM patients were transplanted in our centre between 1995 and 2002. Following ASCT, 35% of patients were in complete remission (CR) and 60% were in partial remission (PR). The median progression-free (PFS) and overall (OS) survival from transplantation were 29.5 and 68.8 months, respectively. Transplant-related mortality (TRM) was 3%. On multivariate analysis, factors associated with significantly shorter OS were lack of CR after transplant (P = 0.002, hazard ratio (HR): 3.1), stage 3 according to ISS (P = 0.001, HR: 3.0) and age at transplant over 60 years (P = 0.035, HR: 2.0). The status of disease before ASCT did not significantly affect PFS and OS after transplantation. We conclude that ASCT is a safe and effective procedure in MM patients, associated with low TRM. The survival after ASCT was dependent on response after ASCT, stage according to ISS and age.     

Survival and outcome of blastoid variant myeloma following treatment with the novel thalidomide containing regime DT-PACE

Blastoid morphology is a rare presenting feature of myeloma which is frequently seen in patients with extramedullary myeloma and is associated with poor clinical outcome. Cell cycle active agents can be effective as treatment for aggressive myeloma and their activity enhanced by using them in combination with the anti-angiogenic agent thalidomide. DT-PACE is an example of such a regimen which we have used to treat 26 relapsed and or refractory patients with extramedullary/blastoid myeloma. The overall response rate (complete response/PR) was 59%, but despite these initial good responses, patients had a short progression free survival (PFS) and overall survival (OS). A subgroup of patients who proceeded to autologous stem cell transplant (ASCT) have a trend towards a better PFS and OS when compared with the group receiving chemotherapy alone (PFS = 10 vs. 3 months P = 0.273 and OS 10 vs. 7 months P = 0.235). Interestingly of the group who received ASCT consolidation three patients remain alive beyond 18 months. In conclusion, the clinical outcome of this group of cases is poor even when treated with the intensive regimen DT-PACE; however, a subgroup can do well if DT-PACE is consolidated by ASCT.     

ThaDD plus high dose therapy and autologous stem cell transplantation does not appear superior to ThaDD plus maintenance in elderly patients with de novo multiple myeloma

Objectives: With the aim to address the issue whether high‐dose therapy (HDT) is required after new drugs combinations to improve outcome of elderly newly diagnosed multiple myeloma (MM) patients, we compared the toxicity and the outcome of ThaDD plus maintenance to those of ThaDD plus HDT‐autologous stem cell transplantation (ASCT). Methods: Sixty‐two patients not eligible for HDT receiving six courses of ThaDD regimen plus maintenance with thalidomide were compared to 26 patients eligible for HDT treated with four courses of ThaDD followed by melphalan 100–200 mg/m² and ASCT. The two groups were matched for the main characteristics except for age favouring the HDT group. Results and conclusions: Complete remission (CR) obtained with ThaDD plus maintenance was 24% whereas it was 57% after ThaDD plus HDT‐ASCT (P = 0.0232). However, after a median follow‐up of 36 months, median time to progression (TTP) and progression free survival (PFS) of the group of patients undergone HDT were not significantly different to those of patients receiving ThaDD plus maintenance (32 vs. 31 months: P = 0.962; 32 vs. 29 months: P = 0.726, respectively). Five‐year overall survival (OS) was 49% in the first group and 46% in the latter one (P = 0.404). As expected, a significantly higher incidence of grade 3–4 neutropenia, thrombocytopenia, infections, mucositis and alopecia were observed in the ThaDD plus HDT group. Our results suggest that in elderly MM patients ThaDD plus HDT, albeit significantly increases CR rate, seems to be equivalent to ThaDD plus maintenance in terms of TTP, PFS and OS. These results challenge the requirement for HDT consolidation in this subset of patients.     

Early post-transplantation positron emission tomography in patients with Hodgkin lymphoma is an independent prognostic factor with an impact on overall survival

The aim of the present study was to investigate the prognostic role of pre- and/or early post-autologous stem cell transplantation (ASCT) ¹⁸F-flourodeoxyglucose (FDG) positron emission tomography (PET) in patients with relapsed/refractory Hodgkin lymphoma. Forty-three consecutive patients were enrolled in this study. FDG-PET/CT was performed following salvage chemotherapy within 6 weeks of undergoing ASCT and at the first month after ASCT. FDG-PET positivity was found in 26 patients before ASCT and in 13 patients after ASCT. The patients who had negative PET scan before or after ASCT had significantly better outcomes in terms of overall survival (OS) and progression-free survival (PFS). Pre- and post-ASCT FDG-PET positivity was found to be independently associated with PFS while post-ASCT FDG-PET was an independent factor with an impact on OS in multivariate analysis. ¹⁸F-flourodeoxyglucose positron emission tomography imaging may be useful in predicting prognosis after ASCT. Furthermore, effective treatment options including allogeneic stem cell transplantation might be considered in patients with positive FDG-PET scan after salvage chemotherapy and ASCT.     

Dose-escalated CHOP and tailored intensification with IFE according to early response and followed by BEAM/autologous stem-cell transplantation in poor-risk aggressive B-cell lymphoma: a prospective study from the GEL-TAMO Study Group

Objectives: The role of high‐dose therapy and autologous stem‐cell transplantation (HDT/ASCT) in the up‐front treatment of poor‐risk aggressive lymphoma is still unknown. We conducted a prospective multi‐centre trial with dose‐escalated CHOP (MegaCHOP) and tailored intensification prior to HDT/ASCT according to early response assessed by CT and gallium scan (Ga⁶⁷S). Patients and methods: Eighty‐six patients with newly diagnosed and Ga‐67 avid aggressive B‐cell lymphoma received MegaCHOP for three courses and were evaluated for response by CT and Ga⁶⁷S. Patients with CT response and negative Ga⁶⁷S received another MegaCHOP cycle followed by BEAM and ASCT. Those patients with positive Ga⁶⁷S or without CT response received salvage treatment with two courses of ifosfamide and etoposide (IFE) followed, whenever response had been achieved, by BEAM and ASCT. Results: Response rate before HDT/ASCT was 85% and, with 34 months of median follow‐up, progression‐free survival (PFS), overall survival (OS) and treatment‐related mortality were 56%, 64% and 7%, respectively. For transplanted patients (81% of the whole series), PFS and OS were 67% and 74%, respectively. No different outcomes were observed between patients achieving an early negative Ga⁶⁷S response treated with MegaCHOP and BEAM/ASCT and patients with mid‐treatment positive Ga⁶⁷S who received IFE prior BEAM/ASCT. Conclusions: This response‐adapted strategy including early treatment modifications prior HDT/ASCT have yielded encouraging PFS and OS in patients with poor‐risk B aggressive non‐Hodgkin’s lymphoma.     

Multicenter phase 2 trial of thalidomide in relapsed/refractory multiple myeloma: adverse prognostic impact of advanced age

Relapsed or refractory multiple myeloma has a poor outlook. Some patients respond to thalidomide; however, criteria for predicting response have not been conclusively identified. We initiated a prospective multicenter phase 2 trial in patients with relapsed/refractory myeloma using thalidomide up to the maximum dose, 800 mg/d. Interferon-alpha-2B (1.5-3.0 x 10(6) U, subcutaneously, 3 times per week) was added at week 12 if disease was responsive or stable. Patients intolerant of interferon continued thalidomide alone. Thalidomide with or without interferon was continued until disease progression. Objectives were to determine toxicity, response rate (RR), progression-free survival (PFS), and overall survival (OS) and to elucidate relevant prognostic factors. We enrolled 75 patients, with median age 64 years (range, 36-83 years). Median individual maximum-tolerated dose of thalidomide was 600 mg/d; 41% reached 800 mg/d. Overall RR was 28%, and 55% stable disease (SD). The only predictor for response was age 65 years or younger (38% versus 17%; P =.043). At 18 months median follow-up, the actuarial median PFS and OS were 5.5 and 14.6 months, respectively. Multivariate analysis for OS demonstrated age exceeding 65 years (median, 9.2 months versus longer than 26 months; P =.011), raised serum lactate dehydrogenase (P =.002), and raised serum creatinine (P =.007) predicted inferior outcomes. Nineteen patients received interferon. Ten discontinued owing to toxicity. Four of 12 patients who received interferon for longer than 4 weeks were converted from SD to partial response. Our findings confirm substantial activity of thalidomide in relapsed/refractory myeloma. Interferon may improve response in selected patients, but is often not tolerated. The inferior outcome demonstrated in those with the identified prognostic factors is important in planning management for such patients.     

Impact of failed response to novel agent induction in autologous stem cell transplantation for multiple myeloma

The aim of this study was to evaluate the impact of the response to induction therapy on the long-term prognosis of multiple myeloma (MM) after autologous stem cell transplantation (ASCT) in the era of novel agents (NAs). A total of 171 patients who were newly diagnosed with MM and underwent early ASCT were analyzed. One hundred ten had a NA-based induction therapy, and 61 patients had a non-NA-based induction therapy. After a median follow-up of 45.4 months, the 4-year overall survival (OS) and progression-free survival (PFS) from transplantation were 60.5 and 25.5 %, respectively, for the NA-based induction group and 54.6 and 15.6 %, respectively, for the non-NA-based induction group. Multivariate analyses revealed that the patients who had NA-based induction had a significantly shorter OS (P?<?0.001) and PFS (P?<?0.001) when at least a partial response (PR) was not achieved. In patients who did not receive NAs before ASCT, lack of at least a PR to induction therapy was not associated with a survival disadvantage. These findings suggest that, unlike pretransplantation induction before NAs, patients who do not respond to induction treatment using NAs may not derive a benefit from ASCT. The relevance of induction failure differs for corticosteroid- and NA-based induction.