Autologous HSCT with novel agent-based induction and consolidation followed by lenalidomide maintenance for untreated multiple myeloma.

Triplet regimen comprising proteasome inhibitors, immunomodulatory drugs, and dexamethasone (DEX) is a recommended induction/consolidation therapy for multiple myeloma (MM) patients eligible for transplant. In this Japanese phase II study conducted from 2017 to 2019, newly diagnosed MM patients aged 20-65 received four induction cycles with bortezomib (Bor), lenalidomide (Len), and DEX (VRD), followed by Bor and high-dose melphalan with autologous stem cell rescue. Subsequently, they underwent four consolidation cycles with carfilzomib, Len, and DEX (KRD), followed by Len maintenance until disease progression. A total of 141 patients were analyzed. In an intent-to-treat population, the complete or better response post induction was 19.9%, rising to 39.7%, 58.9%, and 62.4% after transplant, consolidation, and 1-year maintenance, respectively. With a median follow-up of 38 months, the 3-year progression-free survival (PFS) rate was 83.5% and the 3-year overall survival rate was 92.5%. Severe adverse events (≥grade 3) occurred in ~30% of patients; however, there was no treatment-related mortality. These findings clearly showed the tolerability and effectiveness of this protocol. Nevertheless, patients with high-risk cytogenetics showed a trend toward lower 3-year PFS than those without (77.8% vs. 89.4%, p = 0.051), and ultra-high-risk cytogenetics (≥2 high-risk cytogenetics) had an even worse prognosis, with 61.2% 3-year PFS. To overcome this situation, a more potent treatment strategy incorporating novel agents such as the CD38-antibody should be assessed in future studies.

Twice-weekly induction with ixazomib-lenalidomide-dexamethasone (IRd) combination followed by extended IRd consolidation and lenalidomide maintenance in transplant-eligible patients with newly diagnosed multiple myeloma: Results of the phase 2 study IFM2014-03.

Therapeutic strategies for patients with newly diagnosed multiple myeloma (NDMM) have considerably improved during the last 10 years. The IFM2014-03 trial proposed an all-oral triplet induction/consolidation regimen in transplant-eligible NDMM patients, followed by lenalidomide maintenance. Induction consisted of three 21-day cycles of ixazomib, lenalidomide and dexamethasone (IRd), before high-dose Melphalan with transplant followed by eight 28-day cycles of IRd consolidation before 13 cycles of lenalidomide maintenance. Forty-six patients were enrolled and received at least one dose of therapy, and 39 entered the maintenance phase. The primary end-point was stringent complete response after consolidation, and was achieved in nine patients (20.9%, 90% CI 11.4-33.7; p = 0.998). Ten patients (24.4%) had an undetectable minimal residual disease. The overall response rate was 95.7%. The 3-year progression-free survival was 66.3%. No unexpected toxicities were recorded, and only eight patients suspended from any study drug. Of note, 21 (45.7%) patients reported peripheral neuropathy (PN) (grades 1-2 with no serious adverse events). IRd induction and consolidation with transplant before lenalidomide maintenance shows lower response rates compared to other triplet therapies. It could be an alternative for patients who require an all-oral regimen and/or with pre-existent PN, especially if quadruplet regimens including anti-CD38 antibody are not available.

Clinical outcomes of etoposide and cytarabine as consolidation in elderly patients with primary CNS lymphoma.

BACKGROUND: A consolidation strategy has not been established for transplant-ineligible elderly patients with primary central nervous system lymphoma (PCNSL). In this study, we aimed to retrospectively evaluate the clinical outcomes of etoposide and cytarabine (EA) as consolidation chemotherapy for transplant-ineligible patients with PCNSL following high-dose methotrexate (MTX)-based induction chemotherapy. MATERIALS AND METHODS: Between 2015 and 2021, newly diagnosed transplant-ineligible patients with PCNSL with diffuse large B-cell lymphoma were consecutively enrolled. All enrolled patients were over 60 years old and received EA consolidation after achieving a complete or partial response following induction chemotherapy. RESULTS: Of the 85 patients who achieved a complete or partial response to MTX-based induction chemotherapy, 51 received EA consolidation chemotherapy. Among the 25 (49.0%, 25/51) patients in partial remission before EA consolidation, 56% (n = 14) achieved complete remission after EA consolidation. The median overall survival and progression-free survival were 43 and 13 months, respectively. Hematological toxicities were most common, and all patients experienced grade 4 neutropenia and thrombocytopenia. Forty-eight patients experienced febrile neutropenia during consolidation chemotherapy, and 4 patients died owing to treatment-related complications. CONCLUSION: EA consolidation chemotherapy for transplant-ineligible, elderly patients with PCNSL improved response rates but showed a high relapse rate and short progression-free survival. The incidences of treatment-related mortality caused by hematologic toxicities and severe infections were very high, even after dose modification. Therefore, the use of EA consolidation should be reconsidered in elderly patients with PCNSL.

Anlotinib hydrochloride consolidation after concurrent chemoradiotherapy in stage III non-small-cell lung cancer: a truncated, randomized, multicenter, clinical study (ALTER-L029).

Anlotinib is an antiangiogenic drug that shows good efficacy and safety in patients with advanced non-small-cell lung cancer (NSCLC). This study aimed to explore the efficacy and safety of anlotinib for consolidation therapy in patients with stage III locally advanced, unresectable NSCLC after concurrent chemoradiotherapy (cCRT). This was a randomized, parallel-controlled, open-label, multicenter, phase II trial of patients with unresectable/nonoperated NSCLC treated with cCRT. The participants were randomized 2:1 to the anlotinib or control group. The primary endpoint was progression-free survival (PFS). The secondary endpoints were the disease control rate (DCR) and overall survival. This study was terminated early due to poor recruitment. Nine and two participants were randomly assigned to the anlotinib and control groups, respectively. One participant in the control group was excluded due to taking prohibited medications before the first efficacy evaluation. In the anlotinib group, the median age was 63 (range, 37-74) years. Two participants achieved partial response, six stable disease, and one progressive disease as best response. The DCR was 88.9%. The median PFS was 11.5 months, and the 12-month PFS rate was 33.9%. All related adverse events were grade 1 or 2. Two participants had a dose adjustment during the study. The evaluable data suggest that anlotinib alone was effective and tolerable in consolidation therapy after cCRT in patients with stage III unresectable NSCLC. The results need to be confirmed by a large-sample trial. This clinical trial was registered on www.clinicaltrials.gov (NCT03743129). Registration date: 6 September 2018.

Outpatient consolidation chemotherapy with intermediate dose cytarabine has similar survival and relapses rates in acute myeloid leukemia as compared to high dose cytarabine: A single center analysis.

INTRODUCTION: The last decade has seen advances in delivering outpatient consolidation therapy for acute myeloid leukemia (AML). The standard of care involves high-dose cytarabine or intermediate-dose cytarabine, given twice daily for three alternating days. At the London Regional Cancer Program, we have transitioned the administration of outpatient cytarabine to a once-daily regimen over six consecutive days. The outcomes of a longer duration interval of high-dose cytarabine and intermediate-dose cytarabine is currently unknown. This study aims to assess the feasibility of administering a continuous 6-day protocol of high-dose (HDAC-16) and intermediate-dose cytarabine (IDAC-16) consolidation therapy in the outpatient setting. METHODS: This is a retrospective chart review to analyze AML patients treated with outpatient high-dose or intermediate-dose cytarabine consolidation therapy at the London Regional Cancer Program from January 1, 2019, through November 1, 2022. The primary objective was to determine the outcomes of the 6-day outpatient administration of once daily high-dose cytarabine or intermediate-dose cytarabine. RESULTS: Forty-five patients received 89 cycles of cytarabine as outpatients; males were 55.6% of the total population, with a median age of ~57 years. Our overall 2-year survival of HDAC-16 (57.1%) and IDAC-16 (83.3%) is consistent with the reported literature. There was no difference in delays, relapse rates, and nonrelapse mortality between both HDAC and IDAC groups. The 2-year relapse free survival was 57.1% for HDAC-16 and 66.7% for IDAC-16. CONCLUSION: Outpatient administration of intermediate-dose cytarabine once daily over six consecutive days results in similar overall survival and relapse rates as compared to high dose cytarabine consolidation chemotherapy. Moving to a once daily administration schedule can alleviate logistical and/or accessibility hurdles for outpatient oncology clinics. Prospective randomized trials are needed in this setting to validate our results.

The effectiveness of consolidation chemotherapy in high-risk early-stage cervical cancer patients following concurrent chemoradiation after radical surgery.

OBJECTIVE: Studies determining which early-stage cervical cancer patients with high-risk factors benefit from consolidation chemotherapy after postoperative concurrent chemoradiotherapy (CCRT) are limited and inconsistent. The aim of this study was to evaluate the value of consolidation chemotherapy in early-stage cervical cancer. METHODS: From 2010 to 2019, a retrospective review was conducted among high-risk early-stage cervical cancer patients who were treated with postoperative CCRT or consolidation chemotherapy after postoperative CCRT. Disease-free survival (DFS) and overall survival (OS) were calculated using the Kaplan-Meier method and compared using the log-rank test. RESULTS: A total of 293 patients with early-stage cervical cancer were included in this study. A total of 188 patients were in the consolidation chemotherapy group, and 105 patients were in the postoperative CCRT alone group. The median follow-up was 48.3 months (range: 3-123 months). In the survival analyses, no significant differences in DFS (P = 0.21) or OS (P = 0.15) were observed between the groups. The grade 3-4 leukopenia and neutropenia rates in the consolidation group were higher than those in the concurrent chemoradiotherapy alone group (54.8% vs. 28.6%, P = 0.02; 49.4% vs. 10.5%, P = 0.001, respectively). For patients with ≥2 positive lymph nodes or ≥2 high-risk factors, consolidation chemotherapy significantly improved DFS (P = 0.013 and P = 0.002) and OS (P < 0.001 and P < 0.001) compared with CCRT alone. CONCLUSION: For early-stage cervical cancer, consolidation chemotherapy after postoperative CCRT improved survival outcomes in patients with ≥2 positive lymph nodes or ≥2 high-risk factors.

Safety and feasibility of outpatient high-dose cytarabine and intermediate-dose cytarabine for consolidation therapy in acute myeloid leukemia.

INTRODUCTION: The standard of care consolidation therapy for acute myeloid leukemia is high-dose cytarabine or intermediate-dose cytarabine, which are traditionally given inpatient. At Moffitt Cancer Center, we have moved the administration of high-dose cytarabine and intermediate-dose cytarabine to the outpatient setting through the inpatient/outpatient program. To facilitate outpatient administration, high-dose cytarabine and intermediate-dose cytarabine are given in a shorter interval of every 10 h instead of 12 h. The safety of a shorter duration interval of high-dose cytarabine and intermediate-dose cytarabine is unknown. This study aims to assess the safety and feasibility of administering high-dose cytarabine and intermediate-dose cytarabine consolidation therapy in the inpatient/outpatient setting. METHODS: This is a retrospective chart review to analyze acute myeloid leukemia patients treated with inpatient/outpatient high-dose cytarabine or intermediate-dose cytarabine consolidation therapy at Moffitt Cancer Center from January 1, 2015, through November 1, 2018. The primary objective was to determine the incidence of hospitalization during the inpatient/outpatient administration of high-dose cytarabine or intermediate-dose cytarabine. RESULTS: Two hundred fifty-three of 255 cycles of high-dose cytarabine/intermediate-dose cytarabine were delivered outpatient over the reviewed time period to 118 patients. No patients receiving outpatient high-dose cytarabine/intermediate-dose cytarabine consolidation required hospitalization during chemotherapy. Our incidence of hospitalization (24%) after chemotherapy is consistent with the reported literature. Through the inpatient/outpatient administration of high-dose cytarabine and intermediate-dose cytarabine, 1265 inpatient days were saved with an approximate revenue of $3,135,176 generated in our study period. CONCLUSION: Inpatient/outpatient administration of high-dose cytarabine and intermediate-dose cytarabine is both safe and feasible. Moving high-dose cytarabine/intermediate-dose cytarabine administration to the outpatient setting resulted in significant additional revenue vs. inpatient administration.

Diagnosis and Management of Multiple Myeloma: A Review.

IMPORTANCE: Multiple myeloma is a hematologic malignancy characterized by presence of abnormal clonal plasma cells in the bone marrow, with potential for uncontrolled growth causing destructive bone lesions, kidney injury, anemia, and hypercalcemia. Multiple myeloma is diagnosed in an estimated 34 920 people in the US and in approximately 588 161 people worldwide each year. OBSERVATIONS: Among patients with multiple myeloma, approximately 73% have anemia, 79% have osteolytic bone disease, and 19% have acute kidney injury at the time of presentation. Evaluation of patients with possible multiple myeloma includes measurement of hemoglobin, serum creatinine, serum calcium, and serum free light chain levels; serum protein electrophoresis with immunofixation; 24-hour urine protein electrophoresis; and full-body skeletal imaging with computed tomography, positron emission tomography, or magnetic resonance imaging. The Revised International Staging System combines data from the serum biomarkers ß2 microglobulin, albumin, and lactate dehydrogenase in conjunction with malignant plasma cell genomic features found on fluorescence in situ hybridization-t(4;14), del(17p), and t(14;16)-to assess estimated progression-free survival and overall survival. At diagnosis, 28% of patients are classified as having Revised International Staging stage I multiple myeloma, and these patients have a median 5-year survival of 82%. Among all patients with multiple myeloma, standard first-line (induction) therapy consists of a combination of an injectable proteasome inhibitor (ie, bortezomib), an oral immunomodulatory agent (ie, lenalidomide), and dexamethasone and is associated with median progression-free survival of 41 months, compared with historical reports of 8.5 months without therapy. This induction therapy combined with autologous hematopoietic stem cell transplantation followed by maintenance lenalidomide is standard of care for eligible patients. CONCLUSIONS AND RELEVANCE: Approximately 34 920 people in the US and 155 688 people worldwide are diagnosed with multiple myeloma each year. Induction therapy with an injectable proteasome inhibitor, an oral immunomodulatory agent and dexamethasone followed by treatment with autologous hematopoietic stem cell transplantation, and maintenance therapy with lenalidomide are among the treatments considered standard care for eligible patients.

The effect of consolidation chemotherapy after concurrent chemoradiation on the prognosis of locally advanced cervical cancer: a systematic review and meta-analysis.

To verify the role of consolidation chemotherapy after concurrent chemoradiotherapy for bulky and locally advanced cervical cancer, a meta-analysis was performed. Based on articles published up to Jun 2020 a literature search in PubMed, EMBASE and Cochrane Library was conducted to identify eligible studies. A total of 4 articles consisting of 1659 patients were enrolled. The pooled results revealed that overall survival (OS) of patients treated with consolidation chemotherapy after concurrent chemoradiotherapy (CCRT + CT) was significantly superior to concurrent chemoradiotherapy (CCRT) alone (HR = 0.78, 95% CI: 0.69-0.88, p < .0001). The meta-analysis reviewed that the progression-free survival rate (PFS) of patients treated with CCRT + CT was significantly superior to CCRT alone (HR = 0.80, 95% CI: 0.73-0.87, p < .00001). The pooled results revealed a significant reduction of local recurrence rate for the CCRT + CT group (RR = 0.66, 95% CI: 0.55-0.79, p < .00001). The pooled meta-analysis also showed a significant reduction of distant recurrence rate for the CCRT + CT group (RR = 0.55, 95% CI: 0.44-0.69, p < .00001). The pooled results of grade 3/4 bone marrow suppression were calculated as OR and presented with a 95% CI (OR = 15.85; 95% CI: 9.48, 26.5, p < .00001), indicating patients who received CCRT + CT are more likely to suffer 3/4 bone marrow suppression than those treated with CCRT alone. In conclusion, patients who received chemoradiation with consolidation chemotherapy showed a significantly longer PFS, longer OS, lower local recurrence rate and distant recurrence rate compared to traditional concurrent chemoradiotherapy.Impact statementWhat is already known on this subject? Since CCRT was recommended as the standard treatment for cervical cancer, there was still a 20-30% chance of local recurrence, and 18-25% of distant recurrence for cervical cancer patients. Aiming to completely eradicate potential undetected micrometastases, consolidation chemotherapy came into the area of interest. We conducted a meta-analysis to verify the role of consolidation chemotherapy in cervical cancer.What do the results of this study add? The addition of consolidation CT resulted in a longer overall survival rate (OS) and progression-free survival rate (PFS), mainly due to control of local and distant relapses, especially the latter one. Toxicity followed consolidation CT increased but still clinically manageable.What are the implications of these findings for clinical practice and/or further research? In the future, we need more clinical studies with high quality to verify the role of consolidation CT in cervical cancer, and further to optimise the criteria for it.

Clinical significance of BIM deletion polymorphism in chemoradiotherapy for non-small cell lung cancer.

The standard treatment for locally advanced non-small cell lung cancer (NSCLC) is chemoradiotherapy (CRT) followed by anti-programmed cell death-ligand 1 (anti-PD-L1) treatment. BIM deletion polymorphism induces the suppression of apoptosis resulting from epidermal growth factor (EGFR)-tyrosine kinase inhibitors in EGFR-mutated NSCLC patients. We aimed to examine the effects of BIM polymorphism on CRT and anti-PD-L1/PD-1 treatment in NSCLC patients. In this retrospective study of 1312 patients with unresectable NSCLC treated at Higashi-Hiroshima Medical Center and Hiroshima University Hospital between April 1994 and October 2019, we enrolled those who underwent CRT or chemotherapy using carboplatin + paclitaxel or cisplatin + vinorelbine, or anti-PD-L1/PD-1 treatment. Of 1312 patients, 88, 80, and 74 underwent CRT, chemotherapy, and anti-PD-L1/PD-1 treatment, respectively, and 17.0%, 15.2% and 17.6% of these patients showed BIM polymorphism. Among patients receiving CRT, the progression-free survival was significantly shorter in those with BIM deletion than in those without. In the multivariate analyses, BIM polymorphism was an independent factor of poor anti-tumor effects. These results were not observed in the chemotherapy and anti-PD-L1/PD-1 treatment groups. In in vitro experiments, BIM expression suppression using small interfering RNA in NSCLC cell lines showed a significantly suppressed anti-tumor effect and apoptosis after irradiation but not chemotherapy. In conclusion, we showed that BIM polymorphism was a poor-predictive factor for anti-tumor effects in NSCLC patients who underwent CRT, specifically radiotherapy. In the implementation of CRT in patients with BIM polymorphism, we should consider subsequent treatment, keeping in mind that CRT may be insufficient.

A brief rituximab, bendamustine, mitoxantrone (R-BM) induction followed by rituximab consolidation in elderly patients with advanced follicular lymphoma: a phase II study by the Fondazione Italiana Linfomi (FIL).

Treatment for follicular lymphoma (FL) in the elderly is not well standardized. A phase II, multicentre, single arm trial was conducted in this setting with a brief chemoimmunotherapy regimen. Treatment consisted in four monthly courses of rituximab, bendamustine and mitoxantrone (R-BM) followed by 4 weekly rituximab as consolidation; rituximab maintenance was not applied because the drug was not licensed at the time of enrolment. The primary endpoint was the complete remission rate (CR). Seventy-six treatment-naive FL patients (aged 65-80 and a "FIT" score, according to the Comprehensive Geriatric Assessment) were enrolled. CR was documented in 59/76 patients (78%), partial remission in 12 (16%) and stable/progressive disease in five (6%) with an overall response rate in 71/76 (94%). Median follow-up was 44 months with 3-year progression-free-survival (PFS) and overall-survival of 67% and 92% respectively. Nine deaths occurred, three of progressive disease. The regimen was well tolerated and the most frequent severe toxicity was neutropenia (18% of the cycles). Bcl-2/IGH rearrangement was found in 40/75 (53%) of evaluated patients. R-BM was highly effective in clearing polymerase chain reaction-detectable disease: 29/31 (96%) evaluated patients converted to bcl-2/IGH negativity at the end of treatment. A brief R-BM regimen plus rituximab consolidation is effective and safe in "FIT" elderly, treatment-naïve, FL patients, inducing high CR and molecular remission rates with prolonged PFS.

PD-1 blockade with pembrolizumab for classical Hodgkin lymphoma after autologous stem cell transplantation.

Autologous stem cell transplantation (ASCT) remains the standard of care for patients with relapsed/refractory (RR) classical Hodgkin lymphoma (cHL) who respond to salvage chemotherapy. However, relapse after ASCT remains a frequent cause of treatment failure, with poor subsequent prognosis. Because cHL is uniquely vulnerable to programmed cell death-1 (PD-1) blockade, PD-1 blockade given as consolidation after ASCT could improve ASCT outcomes. We therefore conducted a multicohort phase 2 study of pembrolizumab in patients with RR cHL after ASCT, hypothesizing that it would improve the progression-free survival (PFS) at 18 months after ASCT (primary end point) from 60% to 80%. Pembrolizumab was administered at 200 mg IV every 3 weeks for up to 8 cycles, starting within 21 days of post-ASCT discharge. Thirty patients were treated on this study. The median age was 33 years, and 90% were high-risk by clinical criteria. Seventy-seven percent completed all 8 cycles. Toxicity was manageable, with 30% of patients experiencing at least 1 grade 3 or higher adverse event (AE), and 40% at least 1 grade 2 or higher immune-related AE. Two patients were lost to follow-up in complete remission at 12 months. The PFS at 18 months for the 28 evaluable patients was 82%, meeting the primary end point. The 18-month overall survival was 100%. In conclusion, pembrolizumab was successfully administered as post-ASCT consolidation in patients with RR cHL, and resulted in a promising PFS in a high-risk patient cohort, supporting the testing of this strategy in a randomized trial. This trial was registered at www.clinicaltrials.gov as #NCT02362997.

GIMEMA AML1310 trial of risk-adapted, MRD-directed therapy for young adults with newly diagnosed acute myeloid leukemia.

We designed a trial in which postremission therapy of young patients with de novo acute myeloid leukemia (AML) was decided combining cytogenetics/genetics and postconsolidation levels of minimal residual disease (MRD). After induction and consolidation, favorable-risk patients (FR) were to receive autologous stem cell transplant (AuSCT) and poor-risk patients (PR) allogeneic stem cell transplant (AlloSCT). Intermediate-risk patients (IR) were to receive AuSCT or AlloSCT depending on the postconsolidation levels of MRD. Three hundred sixty-one of 500 patients (72%) achieved a complete remission, 342/361 completed the consolidation phase and were treatment allocated: 165 (48%) to AlloSCT (122 PR, 43 IR MRD-positive) plus 23 rescued after salvage therapy, for a total of 188 candidates; 150 (44%) to AuSCT (115 FR, 35 IR MRD-negative) plus 27 IR patients (8%) with no leukemia-associated phenotype, for a total of 177 candidates. Overall, 110/177 (62%) and 130/188 (71%) AuSCT or AlloSCT candidates received it, respectively. Two-year overall (OS) and disease-free survival (DFS) of the whole series was 56% and 54%, respectively. Two-year OS and DFS were 74% and 61% in the FR category, 42% and 45% in the PR category, 79% and 61% in the IR MRD-negative category, and 70% and 67% in the IR MRD-positive category. In conclusion, AuSCT may still have a role in FR and IR MRD-negative categories. In the IR MRD-positive category, AlloSCT prolongs OS and DFS to equal those of the FR category. Using all the available sources of stem cells, AlloSCT was delivered to 71% of the candidates.This trial was registered at www.clinicaltrials.gov as #NCT01452646 and EudraCT as #2010-023809-36.

Antibiotic use during cytarabine consolidation in acute myeloid leukemia.

Acute myeloid leukemia (AML) patients undergoing consolidation chemotherapy with intermediate or high-dose cytarabine (IDAC/HiDAC) are often placed on prophylactic antibacterials. This practice is largely based on the benefits of prophylaxis (PPX) during induction chemotherapy. However, recent concerns regarding antibacterial prophylaxis have emerged including risk of Clostridioides difficile colitis, medication toxicities, and the potential for fostering multidrug-resistant pathogens. We therefore retrospectively explored whether antibacterial PPX is beneficial during cytarabine consolidation. Adult AML patients who received IDAC/HiDAC at our institution from January 2007 to March 2018 were evaluated for receipt of antibacterial PPX. The primary endpoint was rate of febrile neutropenia (FN); secondary endpoints were rates of unplanned hospitalization, bacteremia, infection from resistant organisms, C. difficile colitis, and death from infection. One hundred twenty patients with data from 229 IDAC/HiDAC cycles were included. Patients who received antibacterial PPX were more often hospitalized during cytarabine cycle 1 (C1) than those who received no PPX. Patients who received PPX had significantly more episodes of bacteremia, in addition to infections from resistant, predominantly Gram-positive organisms during cycle 1 of consolidation than those without PPX. Antibacterial PPX during IDAC/HiDAC consolidation treatment at our institution did not decrease the rates of FN, hospitalization, or bacteremia and was associated with higher risk of infection from drug-resistant bacteria in C1. Prospective studies examining antibacterial prophylaxis during cytarabine consolidation for AML patients are necessary, with strong consideration made for institution-specific protocols.

Full or intensity-reduced high-dose melphalan and single or double autologous stem cell transplant with or without bortezomib consolidation in patients with newly diagnosed multiple myeloma.

OBJECTIVE: A post hoc subgroup analysis of two phase III trials (NCT00416273, NCT00416208) was carried out to investigate the influence of 100/140 and 200 mg/m² melphalan as well as single/double autologous stem cell transplantation (ASCT) on progression-free survival (PFS). Additionally, the effect of bortezomib consolidation on PFS was analyzed. METHODS: Following induction therapy and high-dose melphalan with subsequent ASCT, patients with newly diagnosed multiple myeloma (NDMM) were randomized 1:1 to either four 35-day cycles of bortezomib consolidation (1.6 mg/m² IV on days 1, 8, 15, 22) or observation. RESULTS: Of the 340 patients included in this analysis, 13.5% received 1 × MEL100/140, 22.9% 2 × MEL100/140, 31.2% 1 × MEL200, and 32.4% 2 × MEL200. With higher cumulative melphalan dose, PFS improved (P = .0085). PFS curves of patients treated with 2 × MEL100/140 and 1 × MEL200 were very similar. The superior dose effect of MEL200 over MEL100/140 was non-existent in the bortezomib consolidation arm but pronounced in the observation arm (P = .0015). Similarly, double ASCT was only beneficial in patients without bortezomib consolidation (P = .0569). CONCLUSIONS: Full dose melphalan and double transplantation seem advantageous only as long as patients are not receiving bortezomib consolidation afterwards.

Phase II consolidation trial with anti-Lewis-Y monoclonal antibody (hu3S193) in platinum-sensitive ovarian cancer after a second remission.

OBJECTIVE: To investigate the efficacy and safety of hu3S193, a humanized anti-Lewis-Y monoclonal antibody, as a consolidation strategy in patients with platinum-sensitive recurrent epithelial ovarian cancer who achieved a second complete response after salvage platinum-doublet chemotherapy. METHODS: This single-arm phase II study accrued patients with recurrent epithelial ovarian cancer with Lewis-Y expression by immunohistochemistry who had achieved a second complete response after five to eight cycles of platinum-based chemotherapy. Patients received intravenous infusions of hu3S193, 30 mg/m2 every 2 weeks starting no more than 8 weeks after the last dose of chemotherapy and continuing for 12 doses, until disease progression, or unacceptable toxicity. The primary endpoint was progression-free survival of the second remission. Secondary objectives were safety and pharmacokinetics. RESULTS: Twenty-nine patients were enrolled. Most had a papillary/serous histology tumor (94%), stage III disease at diagnosis (75%), and five (17%) underwent secondary cytoreduction before salvage chemotherapy. Two patients were not eligible for efficacy but were considered for toxicity analysis. Eighteen patients (62%) completed the full consolidation treatment while nine patients progressed on treatment. At the time of analysis, 23 patients (85%) of the eligible population had progressed and seven of these patients (26%) had died. Median progression-free survival of the second remission was 12.1 months (95% CI: 10.6-13.9), with a 1-year progression-free survival of the second remission rate of 50.1%. The trial was terminated early since it was unlikely that the primary objective would be achieved. The most commonly reported treatment-related adverse events were nausea (55%) and vomiting (51%). CONCLUSIONS: Hu3S193 did not show sufficient clinical activity as consolidation therapy in patients with recurrent epithelial ovarian cancer who achieved a second complete response after platinum-based chemotherapy. TRIAL REGISTRATION: NCT01137071.

Allogeneic hematopoietic stem cell transplantation can improve the prognosis of high-risk pediatric t(8;21) acute myeloid leukemia in first remission based on MRD-guided treatment.

BACKGROUND: Pediatric acute myeloid leukemia (AML) with t(8;21) (q22;q22) is classified as a low-risk group. However, relapse is still the main factor affecting survival. We aimed to investigate the effect of allogeneic hematopoietic stem cell transplantation (allo-HSCT) on reducing recurrence and improving the survival of high-risk pediatric t(8;21) AML based on minimal residual disease (MRD)-guided treatment, and to further explore the prognostic factors to guide risk stratification treatment and identify who will benefit from allo-HSCT. METHODS: Overall, 129 newly diagnosed pediatric t(8;21) AML patients were included in this study. Patients were divided into high-risk and low-risk group according to RUNX1-RUNX1T1 transcript levels after 2 cycles of consolidation chemotherapy. High-risk patients were divided into HSCT group and chemotherapy group according to their treatment choices. The characteristics and outcomes of 125 patients were analyzed. RESULTS: For high-risk patients, allo-HSCT could improve 5-year relapse-free survival (RFS) rate compared to chemotherapy (87.4% vs. 61.9%; P = 0.026). Five-year overall survival (OS) rate in high-risk HSCT group had a trend for better than that in high-risk chemotherapy group (82.8% vs. 71.4%; P = 0.260). The 5-year RFS rate of patients with a c-KIT mutation in high-risk HSCT group had a trend for better than that of patients with a c-KIT mutation in high-risk chemotherapy group (82.9% vs. 75%; P = 0.400). Extramedullary infiltration (EI) at diagnosis was associated with a high cumulative incidence of relapse for high-risk patients (50% vs. 18.4%; P = 0.004); allo-HSCT can improve the RFS (P = 0.009). CONCLUSIONS: allo-HSCT can improve the prognosis of high-risk pediatric t(8;21) AML based on MRD-guided treatment. Patients with a c-KIT mutation may benefit from allo-HSCT. EI is an independent prognostic factor for high-risk patients and allo-HSCT can improve the prognosis.

Mutation of CEP72 Gene May Predispose Patients to Hepatotoxicity.

Drug toxicities during treatment of acute lymphoblastic leukemia play a pivotal role in influencing the outcome as certain toxicities may impair treatment compliance. Polymorphisms in CEP72 have been linked to increased incidence of vincristine-induced toxicities, namely peripheral neuropathy. We hypothesize that polymorphisms in the same gene may increase a patient's risk of developing hepatotoxicity when receiving potentially hepatotoxic agents during chemotherapy. This report describes hepatotoxicity that first developed during consolidation in a patient homozygous for the CEP72 risk alleles. Bilirubin levels normalized following dose reduction of 6-mercaptopurine. The patient continues to tolerate maintenance therapy at a reduced dose of 6-mercaptopurine.

Frontline treatment of elderly non transplant-eligible multiple myeloma patients using CyBorD with or without thalidomide-based consolidation: a retrospective multi-centre analysis of real-world data.

Bortezomib in combination with cyclophosphamide and dexamethasone (CyBorD, is a well-established frontline chemotherapy regimen for patients with multiple myeloma, but prospective data on elderly non-transplant eligible patients is limited. A total of 155 patients aged 70 years or older with newly diagnosed multiple myeloma who received at least one cycle of CyBorD chemotherapy in three centres across New Zealand were evaluated. Partial response or better was achieved in 79·4%, of whom 52·9% achieved at least a very good partial response. After a median follow-up of 31·9 months, the median event-free survival (EFS) was 17·0 months (age 70-80 years, 17·7 months; age above 80 years, 8·6 months; P = 0·002). The median overall survival was 45·1 months (age 70-80, 49·8 months; above 80, 33·3 months; P = 0·003). Amongst those who had seven or more cycles of treatment, those who had a pre-planned switch to bortezomib-thalidomide-dexamethasone (VTD) consolidation had a superior median EFS of 25·4 months, compared with 20·3 months in the CyBorD only group (P = 0·028). This is the largest real-world dataset on the efficacy of CyBorD in the elderly population, and pre-planned switch to VTD was associated with better outcomes.

Long-course preoperative chemoradiation versus 5 × 5 Gy and consolidation chemotherapy for clinical T4 and fixed clinical T3 rectal cancer: long-term results of the randomized Polish II study.

BACKGROUND: This trial evaluated whether preoperative short-course radiotherapy and consolidation chemotherapy (CCT) were superior to chemoradiation in rectal cancers with clinical (c)T4 or fixed cT3. Previously, we reported early results showing no differences in the radical surgery rate (primary end point). In the short-course/CCT group, we observed lower acute toxicity of preoperative treatment and better overall survival (OS). We updated results to determine whether the benefit in OS was sustained and to evaluate late complications. PATIENTS AND METHODS: Patients with cT4 or fixed cT3 rectal cancer were randomized either to preoperative 5 × 5 Gy and three cycles of FOLFOX4 or to chemoradiation (50.4 Gy with bolus 5-Fu, leucovorin and oxaliplatin). RESULTS: Patients (N = 515) were eligible for analysis, 261 in the short-course/CCT group and 254 in the chemoradiation group. The median follow-up was 7.0 years. The difference in OS was insignificant [hazard ratio (HR) 0.90; 95% confidence interval (CI) 0.70-1.15; P = 0.38). However, the difference in early OS favouring short-course/CCT previously reported was observed again, being 9% at 3 years (95% CI 0.5% to 17%). This difference disappeared later; at 8 years OS was 49% in both groups. There was no difference in disease-free survival (HR 0.95; 95% CI 0.75-1.19; P = 0.65) at 8 years 43% versus 41% in the short-course/CCT group versus the chemoradiation group, respectively. The corresponding values for cumulative incidences of local failure and distant metastases did not differ and were HR = 1.08, 95% CI 0.70-1.23, P = 0.60, 35% versus 32% and HR = 1.10, 95% CI 0.68-1.23, P = 0.54, 36% versus 34%, respectively. The rate of late complications was similar (P = 0.66), grade 3+ being 11% versus 9% in the short-course/CCT group versus the chemoradiation group, respectively. CONCLUSION: The superiority of preoperative short-course/CCT over chemoradiation was not demonstrated. CLINICAL TRIAL NUMBER: The trial is registered as ClinicalTrials.gov number NCT00833131.