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Objectives: Acquired missense mutations in the BCR::ABL1 kinase domain (KD) may cause tyrosine kinase inhibitor (TKI) treatment failure. Based on mutation‐specific in vitro derived IC50‐values, alternative TKI may be selected. We assessed clinical practice of BCR::ABL1 KD mutation testing, clinical response in relation to IC50‐values, and clinical outcome of tested patients. Methods: Patients from six Dutch CML reference centers and a national registry were included once a mutational analysis was performed. Reasons for testing were categorized as suboptimal TKI response, and primary or secondary TKI resistance. Results: Four hundred twenty analyses were performed in 275 patients. Sixty‐nine patients harbored at least one mutation. Most analyses were performed because of suboptimal TKI response but with low mutation incidence (4%), while most mutations were found in primary and secondary resistant patients (21% and 51%, respectively). Harboring a BCR::ABL1 mutation was associated with inferior overall survival (HR 3.2 [95% CI, 1.7–6.1; p <.001]). Clinically observed responses to TKI usually corresponded with the predicted TKI sensitivity based on the IC50‐values, but a high IC50‐value did not preclude a good clinical response per se. Conclusions: We recommend BCR::ABL1 KD mutation testing in particular in the context of primary or secondary resistance. IC50‐values can direct the TKI choice for CML patients, but clinical efficacy can be seen despite adverse in vitro resistance. [ABSTRACT FROM AUTHOR]

Objectives: In patients with myelodysplastic syndromes (MDS) with >20 transfusions and ferritin levels >1000 μg/L, international guidelines recommend iron chelation therapy (ICT). The study's objective was to determine guideline adherence and the intensity of ferritin monitoring in clinical practice. Methods: We performed an observational population‐based study using the HemoBase Registry, which contains data of all MDS patients diagnosed since 2005 in Friesland, the Netherlands. Clinical information on transfusions, ferritin measurements, ICT, and clinical performance as defined by age ≤ 80 years, Charlson Comorbidity Index <2 and lower‐risk MDS was collected from health records. Results: Two hundred and thirty seven of 292 patients (81.1%) received ≥1 transfusion, and 121 (41.4%) received >20 transfusions. In 57 of these 121 patients (47.1%), ferritin measurements were performed at least once. Clinical performance was significantly associated with monitoring ferritin around the 20th transfusion (RR: 2.49, p =.016). Clinical performance was also associated with initiating ICT (RR: 5.99, p <.001). ICT was offered to 22.3% (n = 25) of eligible patients. Conclusions: In this population‐based study, ferritin levels were measured in <50% of MDS patients who received >20 transfusions, and clinical performance was significantly associated with measuring ferritin. Our study suggests that in heavily transfused MDS patients, ferritin monitoring is primarily based on patients' clinical performance rather than guideline recommendations. [ABSTRACT FROM AUTHOR]

Objectives: Infections are a major cause of morbidity and mortality in patients with myelodysplastic syndromes (MDS). The objective of the MINDSET study was to evaluate haematologists' management of infection prevention in MDS patients using a case vignette study and to assess the availability of guidelines. Methods: We conducted a web‐based, nationwide survey amongst haematologists in the Netherlands between September and December 2021. The survey included a set of case vignettes. In addition, the availability of protocols was evaluated. Results: Sixty responses were obtained (23.6%). These responses were well distributed across hospital types as well as level of experience. No protocols regarding infection prophylaxis specifically for MDS patients were received. In the case vignette of a 75‐year‐old MDS patient, respondents would primarily prescribe infection prophylaxis in case of recurrent infections (96.7%) and neutropenia (75.0% for absolute neutrophil count [ANC] < 0.2 × 109/L and 53.3% for ANC < 0.5 × 109/L), especially in combination with hypomethylating agents (80.0%), lenalidomide (66.7%) or chemotherapy (51.7%). Respondents would predominantly choose antibacterial agents (85.0%), followed by antifungal agents (71.7%). Conclusions: This study showed diverse reasons and considerations of haematologists regarding whether to prescribe infection prophylaxis in MDS patients. Given the seriousness of infections in MDS patients, patient‐tailored recommendations might be valuable in clinical decision‐making. [ABSTRACT FROM AUTHOR]

Background: Ineffective hematopoiesis in patients with myelodysplastic syndromes (MDS) often results in transfusion dependence. The burden of frequent transfusions in the real‐world MDS population is largely unknown. Study design and methods: An observational, retrospective, population‐based study, using the HemoBase registry, was performed including all patients diagnosed with MDS between 2005 and 2017 in Friesland, a province in the Netherlands with approximately 650,000 inhabitants. Detailed clinical information was collected from the electronic health records. Transfusion burden was classified according to the International Working Group 2018 criteria: not transfusion dependent, low (LTB), or high transfusion burden (HTB). Univariate and multivariable regression analyses were performed. Results: Of 292 patients, 136 (46.6%) had a HTB of ≥8 units/16 weeks and 17 (5.8%) had a LTB of 3–7 units/16 weeks. This was present in all types of MDS patients, but patients aged 75–84 years (odds ratio [OR] 4.02, 95% confidence interval [CI]: 1.84–8.82), high‐risk MDS patients (OR 2.88, 95% CI: 1.08–7.68) and MDS‐EB‐2 patients (OR 7.07, 95% CI: 2.17–22.90) were particularly at risk for a HTB. Discussion This study provides a reliable estimate of the transfusion burden in real‐world MDS patients, with almost half of the patients having a HTB. A HTB was observed in all MDS subtypes and both low‐ and high‐risk MDS. Therefore, we conclude that the entire MDS population might benefit from novel agents that reduce the transfusion need and that might have beneficial effects on patient outcomes and healthcare utilization outcomes. [ABSTRACT FROM AUTHOR]

Rituximab‐containing induction followed by autologous stem cell transplantation (ASCT) is the standard first‐line treatment for young mantle cell lymphoma patients. However, most patients relapse after ASCT. We investigated in a randomised phase II study the outcome of a chemo‐immuno regimen and ASCT with or without maintenance therapy with bortezomib. Induction consisted of three cycles R‐CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone), two cycles high‐dose cytarabine, BEAM (carmustine, etoposide, cytarabine, melphalan) and ASCT. Patients responding were randomised between bortezomib maintenance (1·3 mg/m2 intravenously once every 2 weeks, for 2 years) and observation. Of 135 eligible patients, 115 (85%) proceeded to ASCT, 60 (44%) were randomised. With a median follow‐up of 77·5 months for patients still alive, 5‐year event‐free survival (EFS) was 51% (95% CI 42–59%); 5‐year overall survival (OS) was 73% (95% CI 65–80%). The median follow‐up of randomised patients still alive was 71·5 months. Patients with bortezomib maintenance had a 5‐year EFS of 63% (95% CI 44–78%) and 5‐year OS of 90% (95% CI 72–97%). The patients randomised to observation had 5‐year PFS of 60% (95% CI, 40–75%) and OS of 90% (95% CI 72–97%). In conclusion, in this phase II study we found no indication of a positive effect of bortezomib maintenance after ASCT. [ABSTRACT FROM AUTHOR]

Summary: Patients with relapsed/refractory diffuse large B‐cell lymphoma (DLBCL) after, or ineligible for, autologous stem cell transplantation (ASCT) have a dismal prognosis. This phase II study evaluated treatment with R‐PECC (rituximab, prednisolone, etoposide, chlorambucil, lomustine), every 28 days for 4 cycles in 62 patients, followed by radio‐immunotherapy consolidation with 90Y‐ibritumomab tiuxetan in responsive patients. Primary endpoints were failure‐free survival (FFS) and incidence of grade ≥3 adverse events from start of 90Y‐ibritumomab tiuxetan. The overall response rate after R‐PECC was 50%. Twenty‐nine of 31 responsive patients proceeded to 90Y‐ibritumomab tiuxetan. Five out of 15 partial remission patients converted to complete remission after 90Y‐ibritumomab tiuxetan. One‐year FFS and overall survival (OS) from start of 90Y‐ibritumomab tiuxetan was 52% (95% confidence interval [CI], 33–68%) and 62% (95% CI, 42–77%), respectively. One‐year FFS and OS from start of R‐PECC was 28% (95% CI, 17–39%) and 49% (95% CI, 36–61%), respectively. Toxicities of R‐PECC and 90Y‐ibritumomab tiuxetan were mainly haematological. In conclusion, for relapsed DLBCL patients the largely oral R‐PECC regimen achieves promising response rates, combined with an acceptable safety profile. Consolidation with 90Y‐ibritumomab tiuxetan resulted in long‐term response durations in approximately one third of the patients that received it. [ABSTRACT FROM AUTHOR]

Despite a general favourable outcome in limited stage diffuse large B-cell lymphoma (DLBCL), relapses occur in about 10 to 20% of patients. Prognostic models only partially identify patients at risk for relapse. Moreover, it is not known whether the outcome after such a relapse is similar to the outcome after relapse in advanced stages. From January 2004 through December 2012, all newly diagnosed patients with stage I(E) DLBCL were retrospectively analysed from 2 clinical databases to investigate the relapse pattern and outcome in relation to initial treatment and clinical characteristics. In 126 patients (median age 64 years), histologically confirmed stage I(E) DLBCL was diagnosed. With a median follow-up of 53 months (range 5-132 months), 1 progressive disease and 18 relapses occurred. The 5-year time to tumour progression and disease-specific survival were 85% (95% CI 79-91%) and 92% (95% CI 87%-97%), respectively. We observed no significant difference in relapse localization, time to tumour progression, and disease-specific survival between patients treated with abbreviated R-CHOP plus involved field radiotherapy or with 6 to 8 cycles of R-CHOP. Analysis of relapses showed relapse >5 years after initial treatment (late relapse) in 5 of 19 patients (26%). Six of 19 patients (32%) had central nervous system relapse. Three of 11 relapsed cases available for analysis (28%) showed an MYC translocation, suggesting an overrepresentation in the relapse group. Outcome of patients with a relapse was poor with a median survival after relapse of 8 months. Only 1 patient (5%) underwent successful autologous stem cell transplantation. To improve outcome in these patients, early identification of new biological factors such as a MYC translocation or a high risk for CNS dissemination might be helpful. Moreover, treatment of any relapse after stage I disease should be taken seriously. Salvage treatment should be similar to relapses after advanced DLBCL. [ABSTRACT FROM AUTHOR]

Abstract: Objectives: The monitoring of response in chronic myeloid leukemia (CML) is of great importance to identify patients failing their treatment in order to adjust TKI choice and thereby prevent progression to advanced stage disease. Cytogenetic monitoring has a lower sensitivity, is expensive, and requires invasive bone marrow sampling. Nevertheless, chronic myeloid leukemia guidelines continue to recommend performing routine cytogenetic response assessments, even when adequate molecular diagnostics are available. Methods: In a population‐based registry of newly diagnosed CML patients in the Netherlands, all simultaneous cytogenetic and molecular assessments performed at 3, 6, and 12 months were identified and response of these matched assessments was classified according to European Leukemia Net (ELN) recommendations. The impact of discrepant cytogenetic and molecular response classifications and course of patients with additional chromosomal abnormalities were evaluated. Results: The overall agreement of 200 matched assessments was 78%. In case of discordant responses, response at 24 months was consistently better predicted by the molecular outcome. Cytogenetic response assessments provided relevant additional clinical information only in some cases of molecular “warning.” The development of additional cytogenetic abnormalities was always accompanied with molecular failure. Conclusion: We conclude that it is safe to omit routine cytogenetics for response assessment during treatment and to only use molecular monitoring, in order to prevent ambiguous classifications, reduce costs, and reduce the need for invasive bone marrow sampling. Cytogenetic re‐assessment should still be performed when molecular response is suboptimal. [ABSTRACT FROM AUTHOR]

Aims Low-grade follicular lymphoma ( FL) (grade 1/2, FL1/2) has an annual risk of transformation of ≈3%, which is associated with aberrations in CDKN2A/ B, TP53, and MYC. As in diffuse large B-cell lymphoma, high MYC expression in transformed FL ( tFL) might predict a MYC breakpoint. Methods and results We quantified MYC expression by immunohistochemistry and digital analysis in 41 paired biopsies from 20 patients with FL1/2 with subsequent transformation and in four isolated biopsies of tFL. As controls, 28 biopsies of FL1/2 without transformation (median follow-up of 105 months) and nine biopsies of FL3A/B were analysed. In the 20 FL1/2- tFL pairs, MYC expression was significantly higher in tFL than in the initial FL1/2 biopsies (median 54% versus 6%; 7% in FL3A, and 35% in FL3B). MYC breaks ( MYC-R) were detected in eight of 21 (38%) tFLs analysed by fluorescence in-situ hybridization ( FISH), with a median MYC score of 86%. In two of the analysed tFL cases, the translocation was already detected in antecedent FL1/2. MYC partners were immunoglobulin ( IG) loci in three of eight cases (one IGL, one IGH, and one IGK) and non- IG in five of eight cases (two PAX5, one BCL6, and two unknown). Of the eight MYC-R+ cases, six were BCL2+/ MYC+ double-hit, one was BCL2+/ BCL6+/ MYC+ triple-hit, and one was MYC+ single-hit. All three IG- MYC+ cases showed a MYC expression level of >85%, whereas the five cases with a non- IG MYC partner had a wider range of expression (median 68%, range 13-86%). Among the 13 MYC-R− tFLs, two groups with almost dichotomous MYC expression could be observed (three cases showed ≥90% MYC expression), suggesting alternative mechanisms of MYC activation. Conclusions we show an increase in MYC expression from FL1/2 to tFL. MYC breakpoints were present in ≈40% of the cases, which is markedly higher than in de novo DLBCL. MYC expression was uniformly high in cases with an IG- MYC translocation but much more heterogeneous and in part independent of the presence of a MYC break in non- IG- MYC and MYC-negative cases. [ABSTRACT FROM AUTHOR]

Plasmacytoma is characterized by a local accumulation of monoclonal plasma cells without criteria for multiple myeloma ( MM). The current treatment regimen is local radiotherapy. However, more than 50% of patients develop MM within 2 years after treatment. A population-based registry was consulted for the diagnosis of solitary plasmacytoma between 1988 and 2011. Progression to MM and prognostic features for progression to MM were scored, including hypoxia inducible factors ( HIF), vascular endothelial growth factor ( VEGF, also termed VEGFA) and micro-vessel density ( MVD) expression in biopsy material. A total of 76 patients were included, 34% having extramedullary plasmacytoma ( EMP) while 66% had a solitary plasmacytoma of the bone ( SBP). Median follow-up was 89 months, (7-293 months). In Seventy per cent of SBP patients developed MM with a median time to progression of 19 months (5-293). Three patients (12%) with EMP developed MM. High expression of VEGF and HIF-2α (also termed EPAS1) was demonstrated in conjunction with an increased MVD in 66% of the patients. No association could be shown between angiogenesis parameters and progression to MM. In conclusion, this population-based study demonstrates that SBP patients have a higher risk of developing MM following local radiotherapy, indicating that this group might benefit from added systemic chemotherapy. [ABSTRACT FROM AUTHOR]

Combination therapy for longer periods but at low dose might be an effective and tolerable manner to treat patients with relapsed multiple myeloma (MM). We used bortezomib, dexamethasone and low-dose oral cyclophosphamide as an induction regimen, followed by 1 year of maintenance consisting of bortezomib and cyclophosphamide. Relapsed MM patients were treated with six cycles of bortezomib twice weekly, cyclophosphamide 50 mg daily and dexamethasone. Maintenance therapy was given for 1 year. Primary endpoints were toxicity during re-induction and maintenance therapy. Secondary endpoints were response to treatment and progression-free (PFS) and overall survival (OS). This study included 59 patients. Myelosuppression and neuropathy were the most common side effects. Median follow- up was 27.1 (0.46-54.4) months with an overall response of 71%, and a very good partial response or more of 33%. During maintenance, improved responsiveness was observed in 19% of the patients. The median PFS was 18.4 months (range 0.13-43.5) and the median OS was 28.1 months (range 0.13-54.4). In conclusion, our study demonstrates that treatment with bortezomib, dexamethasone and low-dose cyclophosphamide is an effective and manageable regimen. Adding 1 year of maintenance was feasible, with limited side effects and an increased response rate. [ABSTRACT FROM AUTHOR]

Background: The standard therapy in acquired thrombotic thrombocytopenic purpura (TTP) is plasma exchange. In unresponsive TTP, intensification of plasma exchange and immunomodulatory therapy can be initiated but it can be complicated to select for patients that will benefit from intensification. Case Report: We describe two cases of newly diagnosed TTP with a complicated clinical course during initial treatment with plasma exchange. In one case, after an initial response to plasma exchange, a decrease in platelet count was observed on Day 7. The normalized ADAMTS13 activity guided the clinicians in the diagnosis of a concurrent heparin-induced thrombocytopenia due to the heparin lock, used for the indwelling catheter. The other case with TTP clinically deteriorated early during initial treatment. Reevaluation on Day 5, including ADAMTS13 activity, which was undetectably low, supported the clinical decision to intensify the plasma exchange to twice daily and start with the immunomodulating agent rituximab. In both clinically complicated cases measurements of ADAMTS13 activity during plasma exchange proved to be useful in guiding treatment decisions. Conclusion: Serial measurements of ADAMTS13 activity should be considered in patients with newly diagnosed TTP with an unpredictable clinical course during initial therapeutic plasma exchange. These measurements may provide pivotal clinical insights on appropriate patient management. [ABSTRACT FROM AUTHOR]

Many hyperplasias and lymphomas of marginal zone B-cells are associated with infection. We identified six children and one adolescent with cervical lymphadenopathy showing prominent polyclonal nodal marginal zone hyperplasia ( pNMZH) and four adolescents with monoclonal paediatric nodal marginal zone lymphoma ( pNMZL). The clonality status was assessed using BIOMED-2- IG PCR analysis. Haemophilus influenzae was identified in all six cases of pNMZH that could be tested by direct culture ( N = 3) or a very sensitive PCR for the H. influenzae gyrase gene in frozen materials ( N = 5). H. influenzae was not detected in three pNMZLs and 28 non-specific reactive cervical lymph nodes of age-matched controls, except for a single control node that was obtained during oropharyngeal surgery for a cleft palate showing very low copy numbers of H. influenzae. pNMZH patients were younger than pNMZL patients (median age 12 versus 21 years). pNMZH showed a prominent nodular appearance with variable fibrosis without acute inflammation. Within the nodules, the expanded germinal centres and variably sized marginal zones were colonized by activated B-cells with weak expression of IgD and lack of CD10 and/or BCL6 expression. Some areas showed skewed light chain expression in plasma cells (4/5 cases lambda). In four cases tested, this was confirmed by flow cytometry for surface Ig (3/4 cases lambda). In contrast, pNMZL showed more extensive expansion of marginal zones by centrocytoid cells and often expression of BCL2 protein. Several H. influenzae strains are known to interact with the constant part of IgD on human B-cells, leading to their polyclonal proliferation and activation. We speculate that in vivo stimulation of IgD+ marginal zone B-cells by this bacterium may be implicated in this particular lymphadenopathy that should be distinguished from monoclonal pNMZL. Copyright © 2015 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

An observational population-based cohort study was performed to investigate the role of comorbidity on outcome and treatment-related toxicity in patients with newly diagnosed advanced-stage diffuse large B-cell lymphoma ( DLBCL) treated with R- CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone). Data for the clinical characteristics of 154 patients (median age 69 years), including Charlson Comorbidity Index ( CCI), treatment, toxicity and outcome were evaluated. Forty-five percent of the patients had an International Prognistic index ≥3 and 16% had a CCI ≥2. The planned R- CHOP schedule was completed by 84% and 75% reached complete remission ( CR). In those with CCI ≥2, 67% completed treatment with 46% CR. In patients with a CCI <2, overall survival ( OS) after 1, 2 and 5 years was 84%, 79% and 65% respectively and it was 64%, 48% and 48% for those with CCI ≥2. Grade III/IV toxicity was documented in 53%, most frequently febrile neutropenia (27%) and infections (23%). In multivariate analysis CCI ≥2 and IPI ≥3 were independent risk indicators for OS and grade III/ IV toxicity. In conclusion, comorbidity is an independent risk indicator for worse OS in patients with advanced DLBCL treated with R- CHOP by interference with intensive treatment schedules and more grade III/IV toxicity. Future studies are warranted to determine the optimal treatment approach in patients with significant comorbidities. [ABSTRACT FROM AUTHOR]

Summary The efficacy of azacitidine in the treatment of high-risk myelodysplastic syndromes (MDS), chronic myelomonocytic leukaemia (CMML) and acute myeloid leukaemia (AML) (20-30% blasts) has been demonstrated. To investigate the efficacy of azacitidine in daily clinical practice and to identify predictors for response, we analysed a cohort of 90 MDS, CMML and AML patients who have been treated in a Dutch compassionate named patient programme. Patients received azacitidine for a median of five cycles (range 1-19). The overall response rate (complete/partial/haematological improvement) was 57% in low risk MDS, 53% in high risk MDS, 50% in CMML, and 39% in AML patients. Median overall survival (OS) was 13·0 (9·8-16·2) months. Multivariate analysis confirmed circulating blasts [Hazard Ratio (HR) 0·48, 95% confidence interval (CI) 0·24-0·99; P = 0·05] and poor risk cytogenetics (HR 0·45, 95% CI 0·22-0·91; P = 0·03) as independent predictors for OS. Interestingly, this analysis also identified platelet doubling after the first cycle of azacitidine as a simple and independent positive predictor for OS (HR 5·4, 95% CI 0·73-39·9; P = 0·10). In conclusion, routine administration of azacitidine to patients with variable risk groups of MDS, CMML and AML is feasible, and subgroups with distinct efficacy of azacitidine treatment can be identified. [ABSTRACT FROM AUTHOR]

Patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL) after, or ineligible for, autologous stem cell transplantation (ASCT) have a dismal prognosis. This phase II study evaluated treatment with R-PECC (rituximab, prednisolone, etoposide, chlorambucil, lomustine), every 28 days for 4 cycles in 62 patients, followed by radio-immunotherapy consolidation with 90 Y-ibritumomab tiuxetan in responsive patients. Primary endpoints were failure-free survival (FFS) and incidence of grade ≥3 adverse events from start of 90 Y-ibritumomab tiuxetan. The overall response rate after R-PECC was 50%. Twenty-nine of 31 responsive patients proceeded to 90 Y-ibritumomab tiuxetan. Five out of 15 partial remission patients converted to complete remission after 90 Y-ibritumomab tiuxetan. One-year FFS and overall survival (OS) from start of 90 Y-ibritumomab tiuxetan was 52% (95% confidence interval [CI], 33-68%) and 62% (95% CI, 42-77%), respectively. One-year FFS and OS from start of R-PECC was 28% (95% CI, 17-39%) and 49% (95% CI, 36-61%), respectively. Toxicities of R-PECC and 90 Y-ibritumomab tiuxetan were mainly haematological. In conclusion, for relapsed DLBCL patients the largely oral R-PECC regimen achieves promising response rates, combined with an acceptable safety profile. Consolidation with 90 Y-ibritumomab tiuxetan resulted in long-term response durations in approximately one third of the patients that received it., (© 2019 British Society for Haematology and John Wiley & Sons Ltd.)

Plasmacytoma is characterized by a local accumulation of monoclonal plasma cells without criteria for multiple myeloma (MM). The current treatment regimen is local radiotherapy. However, more than 50% of patients develop MM within 2 years after treatment. A population-based registry was consulted for the diagnosis of solitary plasmacytoma between 1988 and 2011. Progression to MM and prognostic features for progression to MM were scored, including hypoxia inducible factors (HIF), vascular endothelial growth factor (VEGF, also termed VEGFA) and micro-vessel density (MVD) expression in biopsy material. A total of 76 patients were included, 34% having extramedullary plasmacytoma (EMP) while 66% had a solitary plasmacytoma of the bone (SBP). Median follow-up was 89 months, (7-293 months). In Seventy per cent of SBP patients developed MM with a median time to progression of 19 months (5-293). Three patients (12%) with EMP developed MM. High expression of VEGF and HIF-2α (also termed EPAS1) was demonstrated in conjunction with an increased MVD in 66% of the patients. No association could be shown between angiogenesis parameters and progression to MM. In conclusion, this population-based study demonstrates that SBP patients have a higher risk of developing MM following local radiotherapy, indicating that this group might benefit from added systemic chemotherapy., (© 2016 John Wiley & Sons Ltd.)

Combination therapy for longer periods but at low dose might be an effective and tolerable manner to treat patients with relapsed multiple myeloma (MM). We used bortezomib, dexamethasone and low-dose oral cyclophosphamide as an induction regimen, followed by 1 year of maintenance consisting of bortezomib and cyclophosphamide. Relapsed MM patients were treated with six cycles of bortezomib twice weekly, cyclophosphamide 50 mg daily and dexamethasone. Maintenance therapy was given for 1 year. Primary endpoints were toxicity during re-induction and maintenance therapy. Secondary endpoints were response to treatment and progression-free (PFS) and overall survival (OS). This study included 59 patients. Myelosuppression and neuropathy were the most common side effects. Median follow-up was 27·1 (0·46-54·4) months with an overall response of 71%, and a very good partial response or more of 33%. During maintenance, improved responsiveness was observed in 19% of the patients. The median PFS was 18·4 months (range 0·13-43·5) and the median OS was 28·1 months (range 0·13-54·4). In conclusion, our study demonstrates that treatment with bortezomib, dexamethasone and low-dose cyclophosphamide is an effective and manageable regimen. Adding 1 year of maintenance was feasible, with limited side effects and an increased response rate., (© 2015 John Wiley & Sons Ltd.)