Mantle cell lymphoma (MCL) presenting in elderly, unfit patients represents a clinical challenge. Front-line 'attenuated' or low-intensity immunochemotherapy is often employed, although outcomes are relatively unexplored. We report outcomes of attenuated immunochemotherapy in 95 patients with MCL across 19 centres in the UK and Ireland considered unfit for full-dose rituximab-bendamustine or rituximab-cyclophosphamide, doxorubicin, vincristine, prednisolone (R-CHOP). Regimens examined were rituximab-cyclophosphamide, vincristine, prednisolone (R-CVP) (n = 19), dose-attenuated R-CHOP (n = 22), dose attenuated rituximab-bendamustine (n = 24) and rituximab-chlorambucil (n = 30). The primary outcome was progressionfree survival (PFS). The secondary outcomes included overall response, overall survival (OS) and toxicity. The median (range) age was 79 (58-89) years and 50% were aged ≥80 years. The median (range) Cumulative Illness Rating Scale-Geriatric score was 6 (0-24). The median PFS for all patients was 15 months [95% confidence interval (CI) 8Á7-21Á2) and median OS was 31Á4 months (95% CI 19Á7-43Á2). By multivariable analysis (MVA), the only clinical factor associated with an inferior PFS was blastoid morphology [hazard ratio (HR) 2Á90, P = 0Á01). Notably, higher treatment intensity (R-CHOP/R-bendamustine composite) provided an independently superior PFS compared with R-CVP/R-chlorambucil (MVA HR 0Á49, P = 0Á02). Factors associated with inferior OS by MVA were Eastern Cooperative Oncology Group Performance Status (HR 2Á14, P = 0Á04), blastoid morphology (HR 4Á08, P = 0Á001) and progression of disease at <24 months status (HR 5Á68, P < 0Á001). Overall, survival after front-line dose-attenuated immunochemotherapy is unsatisfactory. Clinical trials investigating novel agents such as Bruton tyrosine kinase and Bcell lymphoma 2 inhibitors in this specific clinical setting are warranted.

The introduction of tyrosine kinase inhibitors (TKI) has revolutionised the management of patients with chronic myeloid leukemia (CML) over the last twenty years, but despite significant improvements in survival, patients exhibit long-term side effects that impact on quality of life. A major advance in CML management has been the ability to discontinue TKI therapy achieving a treatment-free remission (TFR), yet this option is only available to eligible patients who present with low-risk disease and who subsequently attain deep and sustained molecular responses. A case is described of a patient with CML who self-initiated stopping of TKI therapy when in a less than optimal molecular remission. Despite this action, the patient continues to experience a TFR with prospective close molecular monitoring performed. It is emphasized that this approach may lead to ineffective treatment discontinuation, molecular relapse, and increased patient anxiety. As TFR for patients with CML moves from clinical trials into routine clinical practice, emphasis is placed on adherence to (evolving) guidelines critical to ensure optimal counselling, selection, monitoring, and continued management of patients whether TFR is successful or not.

Bisphosphonates have evolved over the past decades from oral to more potent intravenous preparations. Along with significant paradigm shift in the management of myeloma over the past years, stronger nitrogen-containing bisphosphonates, due to their antiresorptive action on the bones, have found their way as a key and integral part in the management of bone disease in myeloma. Multiple randomized controlled trials have established efficacy of bisphosphonates in reducing skeletal-related events in myeloma. Some well-documented adverse events include acute-phase reactions, esophageal irritation, and osteonecrosis of the jaw. Across all clinical indications, the incidence of inflammatory eye reactions after bisphosphonate infusion ranges from 0.046% to 1%. However, data from myeloma patients are extrapolated from few reported cases in literature with varying management strategies including discontinuation, switching to different forms, and rechallenging with steroid cover. Inflammatory eye reactions can vary from self-limiting conjunctivitis and episcleritis to serious uveitis and vision-threatening orbital inflammation. We present a similar case of a patient with IgG kappa myeloma who developed flu-like symptoms followed by severe orbital inflammation within 48–72 hours after receiving zoledronic acid infusion. The patient was successfully managed with intravenous methyl prednisolone followed by oral tapering dose of steroids and discontinuation of further bisphosphonate therapy. A complete recovery was noted in a week’s time.

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Fig. 1 (A) Brain magnetic resonance imaging depicting acute infarct (arrow). (B) Capillary electrophoresis after fragment length analysis showing a wild-type 263 base-pair peak and mutant 268 base-pair peak in CALR exon 9.