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The text reports on the results from Arm A of the Phase 1/2 DREAMM-6 trial, focusing on the combination of belantamab mafodotin with lenalidomide plus dexamethasone in patients with relapsed/refractory multiple myeloma. The study showed no dose-limiting toxicities and no new safety signals across cohorts, with adverse events consistent with individual agent safety profiles. Ocular events, particularly keratopathy, were the most common Grade 3/4 adverse events, and the overall safety profile was manageable. Efficacy outcomes, such as overall response rate and progression-free survival, were generally similar across cohorts, indicating clinically meaningful anti-myeloma activity. [Extracted from the article]

Purpose: Continuous lenalidomide maintenance treatment after autologous stem cell transplantation delivers improvement in progression free and overall survival among newly diagnosed multiple myeloma patients and has been the standard of care in the UK since March 2021. However, there is scant information about its impact on patients’ day-to-day lives. This service evaluation aimed to qualitatively assess patients receiving lenalidomide treatment at a cancer centre in London, in order that the service might better align with needs and expectations of patients. Methods: We conducted 20 semi-structured interviews among myeloma patients who were on continuous lenalidomide maintenance treatment at a specialist cancer centre in London. Members of the clinical team identified potentially eligible participants to take part, and convenience sampling was used to select 10 male and 10 female patients, median age of 58 (range, 45–71). The median treatment duration was 11 months (range, 1–60 months). Participants were qualitatively interviewed following the same semi-structured interview guide, which was designed to explore patient experience and insights of lenalidomide. Reflexive thematic analysis was used for data analysis. Results: Four overarching themes were as follows: (i) lenalidomide: understanding its role and rationale; (ii) reframing the loss of a treatment-free period to a return to normal life; (iii) the reality of being on lenalidomide: balancing hopes with hurdles; (iv) gratitude and grievances: exploring mixed perceptions of care and communication. Results will be used to enhance clinical services by tailoring communication to better meet patients’ preferences when making treatment decisions. Conclusion: This study highlights that most patients feel gratitude for being offered continuous lenalidomide and perceive it as alleviating some fears concerning relapse. It reveals variations in side effects in different age groups; younger patients reported no/negligible side effects, whilst several older patients with comorbidities described significant symptom burden, occasionally leading to treatment discontinuation which caused distress at the perceived loss of prolonged remission. Future research should prioritise understanding the unique needs of younger patients living with multiple myeloma. [ABSTRACT FROM AUTHOR]

Background: Patients with relapsed/refractory multiple myeloma (RRMM) have a high unmet treatment need. Belantamab mafodotin (belamaf), a first‐in‐class, B‐cell maturation antigen‐binding antibody‐drug conjugate, eliminates myeloma cells through direct cell killing and an anti‐myeloma immune response. Methods: DREAMM‐2 (NCT03525678) was a phase 2, two‐arm, open‐label trial in patients with heavily pretreated RRMM who had three or more prior therapies, were refractory to an immunomodulatory agent and a proteasome inhibitor, and refractory or intolerant to an anti‐CD38 monoclonal antibody. Belamaf was given at 2.5 or 3.4 mg/kg every 3 weeks. The primary end point was overall response rate (ORR); secondary end points included progression‐free survival (PFS), overall survival (OS), safety, ocular symptoms, and health‐related quality of life (HRQOL). Results: This final analysis (cutoff date, March 31, 2022), N = 223, with median follow‐up of 12.5 and 13.8 months, demonstrated an ORR of 32% and 35%, median PFS of 2.8 and 3.9 months, and median OS of 15.3 and 14.0 months in the 2.5 mg/kg and 3.4 mg/kg cohorts, respectively. Median duration of response was 12.5 and 6.2 months. No new safety signals were observed; the most common Grade 3 and 4 adverse events were keratopathy (29% vs. 25%), thrombocytopenia (22% vs. 29%), and anemia (21% vs. 28%). HRQOL outcomes suggest that overall global health status/quality of life, physical and role functioning, and overall disease symptoms were maintained or improved during treatment. Conclusions: This final analysis of DREAMM‐2 confirms that in patients with triple‐class refractory RRMM, single‐agent belamaf results in durable and clinically meaningful responses with a manageable safety profile. Although much progress has been made in the treatment landscape for patients with relapsed/refractory multiple myeloma (RRMM), outcomes remain poor once the disease becomes refractory to multiple therapies. The results of the final analysis of the DREAMM‐2 trial further establish that treatment with single‐agent belamaf results in clinically meaningful responses with a manageable safety profile in patients with RRMM who had received at least three previous lines of therapy. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

The COVID-19 pandemic has had global healthcare impacts, including high mortality from SARS-CoV-2 infection in cancer patients; individuals with multiple myeloma (MM) are especially susceptible to poor outcomes. However, even for MM patients who avoided severe infection, the ramifications of the pandemic have been considerable. The consequences of necessary socio-geographical behavior adaptation, including prolonged shielding and interruptions in delivery of non-pandemic medical services are yet to be fully understood. Using a real-world dataset of 323 consecutive newly diagnosed MM patients in England, we investigated the impact of the COVID-19 pandemic on routes to myeloma diagnosis, disease stage at presentation and relevant clinical outcomes. We demonstrate increasing MM presentations via emergency services and increased rates of bony and extra-medullary disease. Differences were seen in choice of induction therapy and the proportion of eligible patients undertaking autologous stem cell transplantation. Whilst survival was statistically inferior for emergency presentations, significant survival differences have yet to be demonstrated for the entire cohort diagnosed during the pandemic, making extended follow-up critical in this group. This dataset highlights wide-ranging issues facing MM patients consequent of the COVID-19 pandemic, with full impacts for clinicians and policy-makers yet to be elucidated. [ABSTRACT FROM AUTHOR]

2013; 22 (10): 2313 - 20. https://doi.org/10.1002/pon.3284 3 The perspectives of myeloma patients and health care professionals on Minimal Residual Disease (MRD) - Myeloma Patients Europe (mpeurope.org). We show that patients who are MRD negative have a better understanding of the significance compared to MRD positive patients/patients not investigated for MRD. The MRD results were MRD negative for 25 (37%) and MRD positive for 19 (28%) patients. [Extracted from the article]

The COVID-19 pandemic has had global healthcare impacts, including high mortality from SARS-CoV-2 infection in cancer patients; individuals with multiple myeloma (MM) are especially susceptible to poor outcomes. However, even for MM patients who avoided severe infection, the ramifications of the pandemic have been considerable. The consequences of necessary socio-geographical behavior adaptation, including prolonged shielding and interruptions in delivery of non-pandemic medical services are yet to be fully understood. Using a real-world dataset of 323 consecutive newly diagnosed MM patients in England, we investigated the impact of the COVID-19 pandemic on routes to myeloma diagnosis, disease stage at presentation and relevant clinical outcomes. We demonstrate increasing MM presentations via emergency services and increased rates of bony and extra-medullary disease. Differences were seen in choice of induction therapy and the proportion of eligible patients undertaking autologous stem cell transplantation. Whilst survival was statistically inferior for emergency presentations, significant survival differences have yet to be demonstrated for the entire cohort diagnosed during the pandemic, making extended follow-up critical in this group. This dataset highlights wide-ranging issues facing MM patients consequent of the COVID-19 pandemic, with full impacts for clinicians and policy-makers yet to be elucidated. [ABSTRACT FROM AUTHOR]

Three additional patients without prior COVID-19 infection also achieved titers >2500 U/mL at 22 days [6-39] post re-vaccination, compared to titers of 32.7 U/mL (IQR 28.8-36.4) in the same group post-ASCT, demonstrating ability to mount substantial antibody response in the post-ASCT setting. Three patients unexpectedly demonstrated evolving response post-ASCT (pre-ASCT serology measured 26 days [18-36] post-vaccine, time from first vaccine to ASCT 68, 82 and 102 days respectively) which may reflect that humoral response can take several weeks to reach maximum antibody response. Our data suggest that patients who have been vaccinated against COVID-19 prior to ASCT maintain anti-SARS-CoV-2 titers in the immediate post-ASCT setting - a time when patients are considered most vulnerable to infection, and prior to them being offered re-vaccination. [Extracted from the article]

Autologous stem cell transplantation (ASCT) is standard of care in biologically fit, newly diagnosed multiple myeloma (MM) patients, offering better therapeutic outcomes and improved quality of life (QoL). However, with the UK's 1st national lockdown on 23/03/2020, several guidelines recommended deferring ASCT due to risks of infection, with resource limitations forcing some units to suspend ASCT entirely. Such changes to patients' treatment plans inevitably altered their lived experience during these uncertain times with expected impact on QoL. We conducted a qualitative study using semi-structured interviews to gain insight into MM patients' understanding of their disease, initial therapy and ASCT, and their response to therapy changes. A clinical snapshot of how COVID-19 affected the MM ASCT service in a single UK institution is also provided, including changes to chemotherapy treatment plans, timing, and prioritisation of ASCT. Framework analysis identified 6 overarching themes: (1) beliefs about ASCT, (2) perceptions of information provided about MM and ASCT, (3) high levels of fear and anxiety due to COVID-19, (4) feelings about ASCT disruption or delay due to COVID-19, (5) perceptions of care, and (6) importance of social support. Example subthemes were beliefs that ASCT would provide a long-remission/best chance of normality including freedom from chemotherapy and associated side-effects, disappointment, and devastation at COVID-related treatment delays (despite high anxiety about infection) and exceptionally high levels of trust in the transplant team. Such insights will help us adjust our service and counselling approaches to be more in tune with patients' priorities and expectations. [ABSTRACT FROM AUTHOR]

Summary: Depth of response is the critical determinant of prognosis in amyloid light‐chain (AL) amyloidosis. Here, we aim to identify patients who are unlikely to improve response based on analysis of baseline characteristics and 1‐month response. In a multivariate model, difference in involved amyloidogenic and uninvolved serum free light chains (dFLC) at diagnosis (dFLC >400 mg/l, odds ratio [OR] 4.051, p < 0.005) and no response at 1 month (OR 4.787, p < 0.005) were significant predictors of no improvement in response. Only 5% of patients with a dFLC of >400 mg/l and no response at 1 month improved their response (p < 0.005). We suggest that these patients should switch treatment early, subject to their functional status. [ABSTRACT FROM AUTHOR]

A total of 41 (89%) patients started anti-myeloma therapy, three declined, two had not yet commenced treatment; 20 (49%) proceeded to autologous stem cell transplantation (Table SIV). Patients progressing at <6 months from diagnosis were excluded as these patients likely represent evolving disease; similarly those with <6 months of follow-up were also excluded. Smouldering myeloma (SMM) is an asymptomatic stage of multiple myeloma with bone marrow plasma cells >10% or paraprotein >30 g/l, forming a heterogenous group of patients, with variable progression to active myeloma.1 The SMM standard of care is surveillance to identify early progression. [Extracted from the article]

PADIMAC trial Multiple myeloma, autologous stem cell transplantation, high dose therapy, myeloma therapy Keywords: multiple myeloma; autologous stem cell transplantation; high dose therapy; myeloma therapy EN multiple myeloma autologous stem cell transplantation high dose therapy myeloma therapy e33 e37 5 02/14/22 20220215 NES 220215 Current Phase III trials demonstrate the benefit of up-front autologous stem cell transplant (ASCT) as standard of care for transplant-eligible newly diagnosed patients with multiple myeloma.1-3 Deeper responses and achievement of minimal residual disease (MRD) negativity with current triplet and quadruplet treatments4 has questioned timing and role of ASCT with deferral being preferable for some.5,6 Long-term analysis of the EMN02 trial shows that high-risk patients gain most survival benefit from up-front ASCT3 and such risk-stratified approach to ASCT with standard risk patients receiving deferred ASCT, may be acceptable.7 We previously reported primary results of the Phase II PADIMAC trial, which demonstrated a median progression-free survival (PFS) of 17-0 months [95% confidence interval (CI): 10-5-23-2] for 63 patients who achieved a very good partial response (VGPR) or better post induction and stopped treatment until disease progression.8 MRD-positive patients at day 100 had a median PFS of 9-9 months (95% CI: 5-8-23-2) compared to 24-8 months (95% CI: 18-3-34-2) for MRD-negative patients. [Extracted from the article]

Prophylactic strategies (e.g. anti-spike monoclonal antibodies) in patients identified at high-risk of vaccine response failure or in whom vaccination response is suboptimal should be explored. (B) Comparison of post second dose antibody titres in patients who only seroconverted after second dose (n = 19) versus patients with positive response after one dose (n = 69); median (IQR) 54-8 (10-9-299) u/ml versus 1593 (506-2500) u/ml, P < 0-0001. 4 ** There is a borderline association between presence of a post-dose 1 response and response post-dose 2 ( I P i = 0-05), with patients with missing dose 1 responses being more likely to respond post-dose 2. Keywords: multiple myeloma; severe acute respiratory syndrome coronavirus-2; vaccination response; plasma cell disorders; humoral response EN multiple myeloma severe acute respiratory syndrome coronavirus-2 vaccination response plasma cell disorders humoral response e21 e26 6 01/28/22 20220201 NES 220201 We read with interest Avivi I et al i .1 evaluating humoral response to two doses of BNT162b2 mRNA vaccine in multiple myeloma (MM) at manufacturer's dosing interval. [Extracted from the article]

Upfront autologous stem cell transplant (ASCT) for transplant-eligible patients with newly diagnosed multiple myeloma (MM) remains standard of care [[1]]. American society of blood and marrow transplantation, European society of blood and marrow transplantation, blood and marrow transplant clinical trials network, and international myeloma working group consensus conference on salvage hematopoietic cell Transplantation in Patients with Relapsed Multiple Myeloma. Overall, 23 patients (39%) received consolidation and/or maintenance regimens post-ASCT2, a factor shown to improve 2nd PFS in other studies of ASCT2(10,11). [Extracted from the article]

While it may be appropriate to continue G-only mobilization for some MM patients, current guidance should adapt to allow for cyclo-G priming in situations where the risk of additional chemotherapy exposure is deemed to be outweighed by a more optimal PBSC mobilization strategy, even in a post-pandemic environment. With hematology patients being particularly vulnerable to COVID-19 infection, the National Institute of Health and Care Excellence (NICE) issued rapid guidance advising G-CSF only (G-only) priming for PBSC mobilization [[4]]. Despite the dramatic improvement in multiple myeloma (MM) treatment, high-dose therapy and autologous stem cell transplantation (ASCT) continues to offer superior progression free and overall survival in transplant-eligible, newly diagnosed MM (NDMM) [[1]]. Preceding chemotherapy, tumour load and age influence engraftment in multiple myeloma patients mobilized with granulocyte colony-stimulating factor alone. [Extracted from the article]

Introduction: Single-agent belantamab mafodotin (belamaf; BLENREP) demonstrated deep and durable responses in patients with relapsed/refractory multiple myeloma and ≥ 3 prior lines of therapy, including an immunomodulatory agent, proteasome inhibitor, and anti-CD38 antibody (DREAMM-2; NCT03525678). Methods: At the time of this study, STORM Part 2, NCT02336815 (selinexor plus low-dose dexamethasone; sel + dex) was systematically identified as the only feasible comparator to the DREAMM-2 cohort. Matching-adjusted indirect comparisons (MAIC) evaluated efficacy and safety of belamaf (2.5 mg/kg; n = 97) versus sel + dex (80 mg + 20 mg, respectively; n = 123). Populations were weighted for clinically validated effect modifiers and prognostic factors. Outcomes included overall survival (OS), progression-free survival (PFS), duration of response (DoR), overall response rate (ORR), time to response (TTR), and safety. The relative efficacy of belamaf versus standard of care (SoC) on OS was estimated by a Bucher indirect treatment comparison using the MAIC-adjusted hazard ratios (HR) for OS of belamaf (DREAMM-2) versus sel + dex (STORM Part 2) and a HR adjusted for refractoriness to carfilzomib and high-risk cytogenetics of sel + dex (STORM) versus SoC (MAMMOTH). Results: Belamaf demonstrated improved OS (HR 0.53; 95% confidence interval 0.34, 0.83; p = 0.005) and DoR (0.41; 0.21, 0.83; p = 0.013) versus sel + dex. There were no statistically significant differences in ORR, TTR, and PFS. Belamaf had a favorable safety profile for most evaluable hematologic (any-grade, Grade 3–4) and non-hematologic (any-grade) adverse events versus sel + dex. Significantly improved OS was observed with belamaf versus SoC (0.29; 0.16, 0.54; p < 0.001). Conclusion: Single-agent belamaf represents a new treatment option for triple-class refractory patients with RRMM. [ABSTRACT FROM AUTHOR]

Development of antibody response to SARS-CoV-2 following asymptomatic infection in patients with plasma cell disorders on immunomodulatory therapy Keywords: antibody response; COVID-19 disease; multiple myeloma; plasma cell disorders; SARS-CoV-2 EN antibody response COVID-19 disease multiple myeloma plasma cell disorders SARS-CoV-2 857 861 5 09/02/21 20210901 NES 210901 Patients with multiple myeloma and related plasma cell disorders (PCD) are considered extremely vulnerable to SARS-CoV-2 infection due to disease-related impaired humoral and cellular immunity as well as receipt of immunosuppressive therapy.1 Overall mortality from COVID-19 disease in 650 PCD patients across 10 countries was 33%.2 Poor outcomes from COVID-19 disease have resulted in recommendations for modifications to systemic anti-cancer therapy (SACT) to reduce the risk of infection whilst balancing the potential complications of untreated PCD.3 With the rollout of the COVID-19 vaccines, there is urgent need to understand seroconversion in immunocompromised patients for ongoing patient management and recommendation. Positive antibody test post PCR-confirmed infection occurred at a median of 86-5 days compared to 30-5 days for those who tested negative, suggesting a delayed response compared to the general population of 14-28 days.12 Our study and analyses are limited by small number of seropositive patients and those undergoing antibody testing post PCR-diagnosed COVID-19 disease. Patients with positive SARS-CoV-2 antibody test categorised by PCR-positive patients and unexpected antibody test positive patients. [Extracted from the article]

Background: The treatment paradigm for multiple myeloma (MM) continues to evolve with the development of novel therapies and the earlier adoption of continuous treatments into the treatment pathway. Lenalidomide-refractory patients now represent a challenge with inferior progression free survival (PFS) reported to subsequent treatments. We therefore sought to describe the natural history of MM patients following lenalidomide in the real world. Methods: This was a retrospective cohort review of patients with relapsed MM who received lenalidomide-based treatments in the U.K. Data were collected for demographics, subsequent therapies, treatment responses, survival outcomes and clinical trial enrollment. Results: 198 patients received lenalidomide-based treatments at a median of 2 prior lines of therapy at a median of 41 months (range 0.5-210) from diagnosis. 114 patients (72% of 158 evaluable) became refractory to lenalidomide. The overall survival (OS) after lenalidomide failure was 14.7 months having received between 0-6 subsequent lines of therapy. Few deep responses were observed with subsequent treatments and the PFS to each further line was < 7 months. There was a steep reduction in numbers of patients able to receive further treatment, with an associated increase in number of deaths. The OS of patients progressing on lenalidomide who did not enter a clinical trial incorporating novel agents was very poor (8.8 months versus 30 months, p 0.0002), although the trials group were a biologically fitter group. Conclusion: These data demonstrate the poor outcomes of patients failing lenalidomide-based treatments in the real world, the highlight need for more effective treatments. [ABSTRACT FROM AUTHOR]

Summary: Proteasome inhibitors have been associated with thrombotic microangiopathy (TMA) — a group of disorders characterised by occlusive microvascular thrombosis causing microangiopathic haemolytic anaemia, thrombocytopenia and end‐organ damage. To date, carfilzomib‐associated TMA has predominantly been described in relapsed/refractory myeloma patients. We report eight patients with newly diagnosed myeloma who experienced TMA events while receiving carfilzomib on the phase II CARDAMON trial. The first three occurred during maintenance single‐agent carfilzomib, two occurred at induction with carfilzomib given with cyclophosphamide and dexamethasone (KCd) and three occurred during KCd consolidation. At TMA presentation 6/8 were hypertensive; 7/8 had acute kidney injury and in three, renal impairment persisted after resolution of TMA in other respects. The mechanism of carfilzomib‐associated TMA remains unclear, though patients with known hypertension seem particularly susceptible. Given the first three cases occurred during maintenance after a longer than five‐week treatment break, a protocol amendment was instituted with: aggressive hypertension management, carfilzomib step‐up dosing (20 mg/m2 on day 1) at start of maintenance before dose escalation to 56 mg/m2 maximum, and adding 10 mg dexamethasone as premedication to maintenance carfilzomib infusions. No further TMA events occurred during maintenance following this amendment and the TMA incidence reduced from 4·2 to 1·6 per 1 000 patient cycles. [ABSTRACT FROM AUTHOR]

Although small numbers, 1/8 MRD-negative standard risk and 1/3 MRD-negative adverse risk patients became MRD-positive at D100; 4/24 MRD-positive standard risk patients converted to MRD-negative, whereas the only adverse risk patient remained positive at D100 (Table SIX). Autologous stem cell transplantation (ASCT) remains the standard of care for younger and fitter multiple myeloma (MM) patients; however, highly effective induction combination regimens have questioned whether ASCT can be deferred. [Extracted from the article]

(B) PFS in PI refractory patients and 17p deletion patients. Ixazomib, an oral proteasome inhibitor (PI) is approved for the treatment of patients with relapsed and refractory MM in combination with lenalidomide-dexamethasone (IRd). A number of new treatments have been approved for patients with multiple myeloma (MM) and the survival of patients continues to improve. [Extracted from the article]

Belantamab mafodotin (belamaf) demonstrated deep and durable responses in patients with heavily pretreated relapsed or refractory multiple myeloma (RRMM) in DREAMM-2 (NCT03525678). Corneal events, specifically keratopathy (including superficial punctate keratopathy and/or microcyst-like epithelial changes (MECs), eye examination findings with/without symptoms), were common, consistent with reports from other antibody–drug conjugates. Given the novel nature of corneal events in RRMM management, guidelines are required for their prompt identification and appropriate management. Eye examination findings from DREAMM-2 and insights from hematology/oncology investigators and ophthalmologists, including corneal specialists, were collated and used to develop corneal event management guidelines. The following recommendations were formulated: close collaboration among hematologist/oncologists and eye care professionals is needed, in part, to provide optimal care in relation to the belamaf benefit–risk profile. Patients receiving belamaf should undergo eye examinations before and during every treatment cycle and promptly upon worsening of symptoms. Severity of corneal events should be determined based on corneal examination findings and changes in best-corrected visual acuity. Treatment decisions, including dose modifications, should be based on the most severe finding present. These guidelines are recommended for the assessment and management of belamaf-associated ocular events to help mitigate ocular risk and enable patients to continue to experience a clinical benefit with belamaf. [ABSTRACT FROM AUTHOR]

Between 2010 and 2019, 63 MM patients received DT-PACE/ESHAP containing regimens: 42 (67%) for primary refractory, and 21 (33%) for relapsed disease including five patients who had previously received ASCT. One series reports that those able to receive ASCT fared better, suggesting that these patients still benefit from ASCT.12 Our data show a clear distinction in outcomes between patients who were consolidated with ASCT post DT-PACE/ESHAP (mostly primary refractory), I versus i the rest. This is the largest UK dataset of MM patients treated with DT-PACE/ESHAP reported to date, and confirms that even with current novel therapy, traditional infusional regimens retain a role in patients with high risk disease and are well tolerated. Chemotherapy regimens used for induction therapy [all patients and primary refractory patients proceeding to autologous stem cell transplant (ASCT) post ESHAP/PACE].Table SII. [Extracted from the article]

The treatment of relapsed multiple myeloma (MM) is challenging due to increasing disease refractoriness, declining patient performance status and increasing patient co-morbidity.1 The combination of panobinostat, bortezomib and dexamethasone (PAN-Vd) is approved for the treatment of patients with relapsed MM based on the PANORAMA1 trial which compared PAN-Vd to placebo-Vd in patients with relapsed MM who were not previously refractory to bortezomib.2,3 Subgroup analysis showed that the benefit from PAN-Vd was greatest in patients who had received >=2 prior regimens including bortezomib and an immunomodulatory drug (IMiD) where the progression-free survival (PFS) was 12-5 months in the panobinostat arm I versus i 4-7 months in the placebo arm.3 The PANORAMA2 trial evaluated PAN-Vd in 55 heavily pretreated patients with bortezomib-refractory MM and the overall response rate (ORR) was 34-5% with a median PFS of 5-4 months.4 There is little published experience in such heavily pre-treated patients and in UK clinical practice this regimen is often positioned as 5th+ line therapy. Patients who were previously refractory to PI therapy had a significantly shorter PFS and OS than those not previously refractory (median PFS 1-5 months vs. 5-3 months, I P i = 0-008; OS 7-6 months vs. 12-6 months, I P i = 0-040; Fig 1G, H). Overall, our results are inferior to those of the PANORAMA1 study but our patient population is very different; when considering lines of therapy, PI-refractory status and cytopenias, it is likely that only 9% of our patients would have been eligible for PANORAMA1. [Extracted from the article]

Introduction: Patients with relapsed or refractory multiple myeloma (RRMM) represent an unmet clinical need. Belantamab mafodotin (belamaf; GSK2857916) is a first-in-class antibody–drug conjugate (ADC; or immunoconjugate) that delivers a cytotoxic payload, monomethyl auristatin F (MMAF), to myeloma cells. In the phase II DREAMM-2 study (NCT03525678), single-agent belamaf (2.5 mg/kg) demonstrated clinically meaningful anti-myeloma activity (overall response rate 32%) in patients with heavily pretreated disease. Microcyst-like epithelial changes (MECs) were common, consistent with reports from other MMAF-containing ADCs. Methods: Corneal examination findings from patients in DREAMM-2 were reviewed, and the clinical descriptions and accompanying images (slit lamp microscopy and in vivo confocal microscopy [IVCM]) of representative events were selected. A literature review on corneal events reported with other ADCs was performed. Results: In most patients receiving single-agent belamaf (72%; 68/95), MECs were observed by slit lamp microscopy early in treatment (69% had their first event by dose 4). However, IVCM revealed hyperreflective material. Blurred vision (25%) and dry eye (15%) were commonly reported symptoms. Management of MECs included dose delays (47%)/reductions (25%), with few patients discontinuing due to MECs (1%). The first event resolved in most patients (grade ≥2 MECs and visual acuity [each 77%], blurred vision [67%], and dry eye [86%]), with no reports of permanent vision loss to date. A literature review confirmed that similar MECs were reported with other ADCs; however, event management strategies varied. The pathophysiology of MECs is unclear, though the ADC cytotoxic payload may contribute to on- or off-target effects on corneal epithelial cells. Conclusion: Single-agent belamaf represents a new treatment option for patients with RRMM. As with other ADCs, MECs were observed and additional research is warranted to determine their pathophysiology. A multidisciplinary approach, involving close collaboration between eye care professionals and hematologist/oncologists, is needed to determine appropriate diagnosis and management of these patients. Trial Registration: ClinicalTrials.gov Identifier, NCT03525678. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Real-world assessment of the clinical impact of symptomatic infection with severe acute respiratory syndrome coronavirus (COVID-19 disease) in patients with multiple myeloma receiving systemic anti-cancer therapy Keywords: COVID-19; multiple myeloma; systemic antic-cancer therapy EN COVID-19 multiple myeloma systemic antic-cancer therapy e83 e86 4 07/20/20 20200715 NES 200715 Infection with the novel coronavirus SARS-CoV-2, resulting in an acute respiratory disease (COVID-19), is the cause of the current pneumonia pandemic, with a rapid rise in cases being reported in the European Union and UK.1,2 The UK index case was identified on January 31, 2020 and, given the rapid spread and high mortality rate of COVID-19, it is imperative to define the impact on patients with co-existing medical conditions.3 Multiple myeloma (MM), the second-most common haematological malignancy, is a cancer of the mature B-cell lineage, and is associated with both cellular and humoral immune dysfunction that renders patients susceptible to infections, especially of the respiratory tract.4-7 This, coupled with a median age at presentation of 70 years in a population with frequent co-existing medical conditions, means the outcomes of MM patients infected with COVID-19 warrants particular attention. Six patients had clinical/laboratory features of cytokine release syndrome.8,9 One patient was treated with ruxolitinib, but did not survive; one patient received tocilizimab (recovered); and four patients received supportive care only, none of whom survived. [Extracted from the article]

Background: Exercise may improve fatigue in multiple myeloma survivors, but trial evidence is limited, and exercise may be perceived as risky in this older patient group with osteolytic bone destruction.Methods: In this Phase 2 Zelen trial, multiple myeloma survivors who had completed treatment at least 6 weeks ago, or were on maintenance only, were enrolled in a cohort study and randomly assigned to usual care or a 6-month exercise programme of tailored aerobic and resistance training. Outcome assessors and usual care participants were masked. The primary outcome was the FACIT-F fatigue score with higher scores denoting less fatigue.Results: During 2014-2016, 131 participants were randomised 3:1 to intervention (n = 89) or usual care (n = 42) to allow for patients declining allocation to the exercise arm. There was no difference between groups in fatigue at 3 months (between-group mean difference: 1.6 [95% CI: -1.1-4.3]) or 6 months (0.3 [95% CI: -2.6-3.1]). Muscle strength improved at 3 months (8.4 kg [95% CI: 0.5-16.3]) and 6 months (10.8 kg [95% CI: 1.2-20.5]). Using per-protocol analysis, cardiovascular fitness improved at 3 months (+1.2 ml/kg/min [95% CI: 0.3-3.7]). In participants with clinical fatigue (n = 17), there was a trend towards less fatigue with exercise over 6 months (6.3 [95% CI: -0.6-13.3]). There were no serious adverse events.Conclusions: Exercise appeared safe and improved muscle strength and cardiovascular fitness, but benefits in fatigue appeared limited to participants with clinical fatigue at baseline. Future studies should focus on patients with clinical fatigue.Clinical Trial Registration: The study was registered with ISRCTN (38480455) and is completed. [ABSTRACT FROM AUTHOR]

Summary: 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. [ABSTRACT FROM AUTHOR]

A majority of patients experienced at least one grade >=3 AE (21 patients [87-5%]) and/or serious adverse event (SAE) (13 patients [54-2%]). The SAEs experienced by >=5% of patients were thrombocytopenia (three patients [12-5%]), injection site reaction, acute kidney injury, and malaise (two patients [8-3%] in each PT). The most common treatment-emergent AEs, experienced by >=30% patients, were injection site reaction (19 patients [79-2%]), fatigue (15 patients [62-5%]), anemia (12 patients [50-0%]), thrombocytopenia (11 patients [45-8%]), nausea (ten patients [41-7%]), diarrhea (nine patients [37-5%]), and decreased appetite (eight patients [33-3%]). Patients had a median of 6 (range 3-9) prior lines of therapy and were refractory to immunomodulatory drugs (IMiDs, 46% of patients), proteasome inhibitors (54%), IMiDs and proteasome inhibitors (38%), and daratumumab (33%) (Supplementary Table 1). [Extracted from the article]

Summary: 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). [ABSTRACT FROM AUTHOR]

The article highlights the clinical benefit of depth of response for Relapsed and Refractory Multiple Myeloma (RRMM). It discussed the Prognostic factors in multiple myeloma (MM) including genetic abnormalities, International Staging System (ISS), and depth of response; and mentions the prognostic significance of cytogenetics in RRMM.

The article focuses on a study which aims to investigate bortezomib monotherapy for up to 8 cycles in patients who receive upfront autologous stem cell transplantation after non-bortezomib containing induction regimens. Information about disease response and treatment tolerability as well as minimal residual disease status is presented.

The article focuses on the feasibility in the use of the inhibitor Panobinostat in patients with relapsed multiple myeloma (MM) alongside dexamethasone and bortezomib. It talks about the clinical trial for progression-free survival (PFS) in patients going through disease relapse. It tells about the need to improve the efficiency of the drugs Dexamethasone, Bortezomib and Thalidomide alongside the inhibitor.