Impact of timing of stem cell return following high dose melphalan in multiple myeloma patients with renal impairment: a single center experience.

High dose melphalan (HDM) followed by autologous stem cell transplantation (ASCT) remains the standard consolidation in transplant eligible multiple myeloma (MM) patients. The timing between HDM administration and hematopoietic stem cell return (HSCR) varies among institutions, with a 'rest period' of 48 hours (h) employed by some for patients with renal impairment (RI). We investigated the differences in hematopoietic recovery and HDM toxicity between MM patients with RI who had HSCR after 24 vs 48 h from HDM. Fifty MM patients with RI (48 h group; n = 31 and 24 h group; n = 19) were included. No statistically significant differences were noted in surrogates for hematopoietic recovery and HDM toxicity between both groups. Only one death occurred in the 24 h group. No patients required renal replacement therapy. Therefore, a 24 h period between HDM and AHSC infusion appears safe for MM patients with RI.

Real-world, single-center experience of SARS-CoV-2 vaccination in immune thrombocytopenia.

BACKGROUND: Immune thrombocytopenic purpura (ITP) relapse following vaccination remains poorly reported in the adult population. OBJECTIVES: This report details real world data from the largest single-center cohort of ITP relapse following severe acute respiratory syndrome (SARS-CoV-2) vaccination. METHODS: The vaccination status of 294 patients under active follow-up was reviewed. A total of 17 patients were identified resulting in an incidence of ITP relapse following SARS-CoV-2 vaccination in this cohort of 6.6% and an incidence of newly diagnosed ITP following SARS-CoV-2 vaccination of 1.4%. RESULTS: Patients were noted to develop marked deviation of platelet count from baseline following vaccination (P =< .0001). Fourteen patients had a prior diagnosis of ITP and median follow-up following diagnosis was 4 years (range 0-45 years). Days from vaccination to presentation ranged from 2-42 (median 14) and the follow-up period was 34 weeks. Fifteen patients (88%) presented with symptoms and all 17 patients developed symptoms during the follow-up period. Nine patients (53%) received a second dose of vaccine during the follow-up period with seven patients (78%) requiring therapeutic support to facilitate second vaccination. Decision to treat patients was multi-factorial and aimed at decreasing bleeding symptoms and obtaining a platelet count >30 × 109 /L. Sixteen patients (94%) required therapeutic intervention and at the end of the follow-up period, four patients (24%) remained unresponsive to treatment with a platelet count <30 × 109 /L. CONCLUSION: Vaccination of ITP patients continues to have important clinical benefit; however, recommendations for patients who relapse remain lacking. This report outlines the real-world patient outcomes in the era of widespread SARS-CoV-2 vaccination.

Rapid response to single agent daratumumab is associated with improved progression-free survival in relapsed/refractory AL amyloidosis.

Background: Daratumumab is a monoclonal antibody, which targets CD38; an antigen expressed on malignant plasma cells in AL amyloidosis thus providing a rationale for its use.Method: Patients treated with daratumumab monotherapy (2016-2019) for relapsed/refractory systemic AL amyloidosis were identified from the database at the UK National Amyloidosis Centre.Results: Of 50 evaluable patients, haematological responses at 3 months were: CR - 19 (38%), VGPR - 14 (28%), PR - 9 (18%) and no response - 8 (16%). Median time to response was 1 (1-6) month. Of assessable patients, cardiac, renal and hepatic responses were seen in 43.8%, 25.0% and 0% of patients whilst progression occurred in 25.0%, 12.5% and 37.5% respectively. Patients achieving a CR had longer median OS (not reached vs. 22.7 months [95% CI 17.0-28.4 months]) (p = .036). Furthermore, patients achieving a rapid response (at 1 month) had a longer median PFS (not reached vs. 9 months [95% CI 5.8-12.2 months]) (p = .013).Conclusion: Daratumumab monotherapy is effective in multiply-relapsed systemic AL amyloidosis and should be considered, if available, in patients who have not received prior daratumumab therapy. Responses are achieved rapidly and overall response rate was 84%. CR predicts overall survival whilst speed of response is predictive of a longer PFS.

Use of ixazomib, lenalidomide and dexamethasone in patients with relapsed amyloid light-chain amyloidosis.

With improving outcomes in amyloid light-chain (AL) amyloidosis, there is a need to study novel agents in this setting. We report outcomes of 40 patients with relapsed AL amyloidosis treated with ixazomib + lenalidomide + dexamethasone (IRd). Haematological responses were assessed on an intention-to-treat basis at three months: complete response (CR) - 8 (20·5%), very good partial response (VGPR) - 8 (20·5%), partial response (PR) - 7 (17·9%) and no response (NR) - 16 (41·0%). One patient had missing data. Six patients subsequently improved response. Best responses were: CR - 10 (25·6%), VGPR - 8 (20·5%), PR - 7 (17·9%), NR - 14 (35·9%). Cardiac and renal organ responses occurred in 5·6% and 13·3% respectively. Median progession-free survival (PFS) was 17·0 months (95% CI 7·3-20·7 months), improving to 28·8 months (95% CI 20·6-37·0 months) in those achieving CR/VGPR. Median overall survival was 29·1 months (95% CI 24-33 months). Serious adverse events were seen in 14 (35·0%) patients inclusive of 15 admissions due to: infection (6/15, 40·0%), fluid overload (5/15, 33·3%), cardiac arrhythmia (2/15, 13·3%), renal dysfunction (1/15, 6·6%) and anaemia (1/15, 6·6%). In summary, IRd is an oral treatment option with a manageable toxicity profile leading to deep responses in 47% of patients with relapsed AL amyloidosis.

Ambulatory approach to cancer care. Part 3: starting and maintaining the service and its challenges and benefits.

This is the final article in a three-part series. Previous articles discussed the patient experience and the enhanced roles of nurses and the multidisciplinary team (MDT) and their role in safety within ambulatory care (AC) at a major London teaching hospital. There is understandably apprehension when starting a new service and embarking on a new healthcare concept. The challenges of starting and maintaining an AC service are multifaceted. Common questions posed to this London teaching hospital concern the challenges of opening and maintaining a new service and the savings it will produce. There are many indirect savings and benefits to an ambulatory service, although the value of a positive patient experience cannot be measured in monetary terms.

Carfilzomib is an effective upfront treatment in AL amyloidosis patients with peripheral and autonomic neuropathy.

Bortezomib is standard treatment in AL amyloidosis (AL), but is contraindicated in patients with significant neuropathy. Carfilzomib, a second-generation proteosomal inhibitor, results in a lower incidence of neuropathy than bortezomib, but data in AL is scant. We report a cohort of five AL patients treated with upfront carfilzomib. All had cardiac, peripheral and autonomic neuropathy at presentation. All achieved at least a very good partial haematological response. There was no worsening in cardiac function, peripheral or autonomic neuropathy. Carfilzomib is an effective upfront treatment option in AL patients with peripheral and/or autonomic neuropathy (without severe cardiac or renal involvement).

Atypical haemolytic uraemic syndrome in the eculizumab era: presentation, response to treatment and evaluation of an eculizumab withdrawal strategy.

The complement inhibitor, eculizumab, has revolutionised the management of atypical haemolytic uraemic syndrome (aHUS), although the optimum treatment duration is debated. Twenty-two cases of acute aHUS managed with eculizumab were retrospectively reviewed, including outcomes after eculizumab withdrawal. Although 41% had an associated complement genetic abnormality, mutation status did not affect severity of clinical presentation. Sixty-four percent required renal replacement acutely, with a high incidence of nephrotic range proteinuria (47%). Eculizumab followed a median of 6 days of plasma exchange. After a median duration of therapy of 11 weeks (range 1-227), haematological recovery was seen in 100%, while 81% achieved at least partial renal recovery (median increase in estimated glomerular filtration rate (eGFR) 49 ml/min/1·73 m2 ). At median duration of follow-up of 85 weeks (range 4-255), 54·5% had eGFR ≥ 60 ml/min/1·73 m2 , 27% had CKD, 14% were on dialysis, and 4·5% had died. Eculizumab was withdrawn in 59% (13/22) cases following complete haematological and renal recovery. Three of these 13 patients (23%) subsequently relapsed, with defined triggers in 2/3, but all made a full recovery with rapid resumption of eculizumab. There was a significant association between higher presenting creatinine and poorer renal outcomes. A strategy of eculizumab withdrawal in selected cases is both safe and cost effective.

Comparison of Rituximab originator (MabThera) to biosimilar (Truxima) in patients with immune-mediated thrombotic thrombocytopenic purpura.

Immune thrombotic thrombocytopenic purpura (iTTP) is an acute, multisystem thrombotic microangiopathy mediated by ADAMTS13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13) autoantibodies. Immunosuppression with anti-CD20 therapy is the mainstay of treatment. MabThera's patent has now expired and biosimilars have been approved. Eighty-four consecutive patient episodes over 2 years, prior to and following our switch to Truxima are presented. Day 1 (D1), Day 28 (D28) and 3-month platelet counts, ADAMTS13 activity, and CD19 levels, adverse reactions and infective complications were recorded. Platelet counts were not significantly different between acute MabThera and Truxima treatment (D1 P = 0.085, D28 P = 0.77, 3 months P = 0.71) and electively (D1 P = 0.79, D28 P = 0.68, 3 months P = 0.99). ADAMTS13 recovery also was not significantly different acutely (D1 P = 0.99, D28 P = 0.27, 3 months P = 0.26) and electively (D1 P = 0.59, D28 P = 0.61, 3 months P = 0.34). CD19% depletion at D1 and 3 months was not significantly different acutely (D1 P = 0.52, 3 months P = 0.56) and electively (D1 P = 0.22, 3 months P = 0.19). Infusion reactions and infective complications were comparable with both therapies. This is the first series of the Rituximab biosimilar Truxima to be reported in iTTP, demonstrating equivalence to MabThera in terms of ADAMTS13 recovery, CD19 depletion, and platelet count at D28 and 3 months post-administration, with comparable infusion and infective complications. The financial benefit of the biosimilar anti-CD20 is considerable.

Ambulatory approach to cancer care. Part 2: the role of nurses and the multidisciplinary team and safety.

Ambulatory care (AC) involves providing inpatient chemotherapy and supportive care as an outpatient service. Nurses and the multidisciplinary team (MDT) have a major role in this. AC at a major London teaching hospital trust is a nurse-led service, headed by specialist cancer nurses with excellent knowledge of the needs and priorities of patients undergoing intensive treatment. An experienced MDT, including administrative support, maintains safety and continuity of care. The nurses, MDT and patient work closely to promote the patient's wellbeing, self-management and trust. A scenario is analysed in this article to illustrate potential concerns around a patient's safety and suitability for AC. This is the second article of a three-part series; the previous article discussed AC at a major London teaching hospital and improving the patient experience.

Ambulatory approach to cancer care. Part 1: the patient experience.

Ambulatory care (AC) is an approach within which inpatient chemotherapy regimens and supportive care are delivered in an outpatient service. Patients receive their treatments and supportive care daily in AC and stay at a nearby hotel or their home, rather than in an inpatient bed. A systematic literature search found a growing amount of literature on AC and the specific regimens used. However, little was found on AC with regard to the patient experience, safety, the benefits and challenges of running an AC service. This series of three articles is based on the authors' experiences of working within an AC service at a major London teaching hospital. The authors discuss the approach and explore how it can improve the patient experience. They look at the roles of the multidisciplinary team and their part in patient safety, and the benefits, challenges and cost considerations of an AC service.