Abstract
Background
Neutropenia may limit the use of valganciclovir treatment for cytomegalovirus (CMV) infection following hematopoietic cell transplant (HCT). A phase 2 study indicated efficacy of ...maribavir with fewer treatment-limiting toxicities than valganciclovir.
Methods
In this multicenter, double-blind, phase 3 study, patients with first asymptomatic CMV infection post-HCT were stratified and randomized 1:1 to maribavir 400 mg twice daily or valganciclovir (dose-adjusted for renal clearance) for 8 weeks with 12 weeks of follow-up. The primary endpoint was confirmed CMV viremia clearance at week 8 (primary hypothesis of noninferiority margin of 7.0%). The key secondary endpoint was a composite of the primary endpoint with no findings of CMV tissue-invasive disease at week 8 through week 16. Treatment-emergent adverse events (TEAEs) were assessed.
Results
Among patients treated (273 maribavir; 274 valganciclovir), the primary endpoint of noninferiority of maribavir was not met (maribavir, 69.6%; valganciclovir, 77.4%; adjusted difference: −7.7%; 95% confidence interval CI: −14.98, −.36; lower limit of 95% CI of treatment difference exceeded −7.0%). At week 16, 52.7% and 48.5% of patients treated (maribavir and valganciclovir, respectively) maintained CMV viremia clearance without tissue-invasive disease (adjusted difference: 4.4%; 95% CI: −3.91, 12.76). With maribavir (vs valganciclovir), fewer patients experienced neutropenia (16.1% and 52.9%) or discontinued due to TEAEs (27.8% and 41.2%). Discontinuations were mostly due to neutropenia (maribavir, 4.0%; valganciclovir, 17.5%).
Conclusions
Although noninferiority of maribavir to valganciclovir for the primary endpoint was not achieved based on the prespecified noninferiority margin, maribavir demonstrated comparable CMV viremia clearance during post-treatment follow-up, with fewer discontinuations due to neutropenia.
Clinical Trials Registration. NCT02927067 AURORA.
Noninferiority of maribavir to valganciclovir was not met for the primary endpoint of CMV viremia clearance at study week 8. However, maribavir had comparable post-treatment CMV viremia clearance to valganciclovir, and was associated with a lower incidence of treatment-limiting neutropenia.
Graphical Abstract
Graphical Abstract
Double or triple hit Lymphomas (DHL) are characterized by translocation rearrangements of C-MYC with the addition of BCL2 and/or BCL 6, which are associated with a poor outcome due to their genetic ...complexity . Clinical controversies remain regarding the optimum treatment for patients with DHL due to lack of consensus regarding the optimal management and also age and frailty being a significant obstacle, limiting the role of dose-escalated or intensified therapy. Literature review suggests overall median survival for DHL patients is from 0.2-1.5years2. We report our single centre experience of treating this patient group.
Materials & Methods:
This single centre retrospective study evaluated the outcome of DHL patients who underwent various lines of treatment including standard R-CHOP chemotherapy, more intensive chemotherapy regimens and allogeneic stem cell transplantation (AlloSCT). Diagnosis of DHL was as per the 2008 WHO classification. Statistical analysis was performed by using SPSS 23®.
Results:
Our study included fourteen patients (9M; 5F) with a median age 60.5 years (range 33-65). 4 patients had stage 2B disease, 3 had stage 3B and 7 had 4B disease. R-CHOP chemotherapy only was commenced as first line treatment in 4 patients, R-CHOP plus intrathecal chemotherapy was given to 2 patients and 1 patient received R-CEOP. 5 patients received intensive chemotherapy with R-CODOX-M/R-IVAC where as one patient received EPOCH in a different centre prior to transfer. 1 patient received radiotherapy only.
10 patients were in complete remission following first line chemotherapy. One patient progressed following first line treatment and was managed palliatively. One patient relapsed whilst awaiting AlloSCT and was given mini-DEX BEAM salvage chemotherapy prior to transplant. One patient had a partial response to first line treatment and was given further rituximab but had progressive disease and was also managed palliatively. One patient had progressive disease and received GDP chemotherapy.
8 patients underwent AlloSCT with BEAM Alemtuzumab conditioning with cyclosporine as GvHD prophylaxis (6 unrelated and 2 sibling donors). The mean overall survival from starting treatment for DHL for the non-transplant cohort was 18.5 months (Range: 0.5 to 36.5) and the median OS was 8.3 months (Range: 4 to 12.6) as compared to mean overall survival of 44.2 months (Range: 22.2 to 66.35) in the transplant cohort with median overall survival not reached (p value: 0.46, Log Rank). In our patients, there was no progression after 3 months from Allo SCT. One patient progressed 6 weeks and died 8 weeks post AlloSCT, whereas two patients progressed 12 weeks and died 14 weeks post AlloSCT. In the cohort who did not undergo AlloSCT, 3 patients have died and two remain in complete remission and 1 patient is undergoing salvage chemotherapy for refractory disease.
Conclusion:
Our single centre experience of limited number of patients with DHL suggests AlloSCT as a consolidative treatment in first complete remission, may offer survival benefit as compared to no consolidation. Our data also shows no progression of DHL 3 months post AlloSCT highlighting the potential graft versus lymphoma effect. This requires further evaluation in a larger cohort to confirm our preliminary findings and identify potential biomarkers of best response. Confirmation of this result in larger cohort will identify the role of AlloSCT in DHL and enable to reach consensus in the DHL management.
Kishore:celgene: Other: travel grant.
In multiple myeloma (MM), improving our understanding of routine clinical practice and the effectiveness of agents outside of clinical trials is important. TOURMALINE-MM1 data resulted in approval of ...ixazomib for MM patients who have received ≥ 1 prior therapy.
UVEA-IXA comprised a retrospective chart review in the early access program, and a prospective 1-year follow-up period. Eligible patients had had a biochemical and/or symptomatic relapse after 1-3 prior lines of therapy; no anti-MM therapy for > 3 cycles at the start of ixazomib therapy; and an Eastern Cooperative Oncology Group performance score of 0-2. Lenalidomide- or proteasome inhibitor (PI)-refractory patients were ineligible. Primary endpoints were response and progression-free survival (PFS).
Of 357 enrolled patients, 309 were evaluable; most patients received ixazomib alongside lenalidomide (98%) and dexamethasone (97%); 61% had received 2-3 prior lines of therapy. Median PFS was 15.6 months (95% confidence interval CI: 12.0-20.6) in all evaluable patients, and 19.6 (95% CI: 12.1-27.0) and 13.9 (95% CI: 10.1-18.1) months in patients who received 1 and ≥ 2 prior lines of therapy, respectively. The overall response rate was 67% in all evaluable patients, and 72% and 63%, respectively, in patients who received 1 and ≥ 2 prior lines of therapy. Median overall survival was 35.5 months. The ixazomib safety profile was consistent with previous reports.
This study supports ixazomib-based therapy as an effective and tolerable treatment in the real-world. Outcomes were favorable in patients with 1 or ≥ 2 prior lines of therapy who were not lenalidomide- or PI-refractory.
Background
Although the median age of patients with newly diagnosed multiple myeloma (MM) is 70-74 years, recruitment of frail older patients to clinical trials is poor. The International Myeloma ...Working Group (IMWG) frailty score predicts survival, adverse events and treatment tolerability using age, the Katz Activity of Daily Living, the Lawton Instrumental Activity of Daily Living, and the Charlson Comorbidity Index, rather than age alone. Despite IMWG score prognostic biomarker capability, to date no evidence exists of its predictive biomarker potential. The UK-MRA Myeloma Risk Profile (MRP) has also been shown in both clinical trial and real-world populations to be a prognostic biomarker in transplant ineligible patients but prospective comparisons of the two scores have not been previously conducted.
Study Design/Methods
The FiTNEss trial (Myeloma XIV, NCT03720041, Figure 1A) is a UK-MRA phase III, multi-centre, randomised controlled trial for newly diagnosed MM patients not suitable for stem cell transplant. The primary objectives are
1) to compare early treatment cessation (<60 days from randomisation) between patients randomised to standard (reactive) and frailty-adjusted (adaptive, based on IMWG score) induction therapy delivery with the triplet ixazomib, lenalidomide and dexamethasone (IRd)
2) to compare progression free survival for maintenance lenalidomide plus placebo (R) and lenalidomide plus ixazomib (IR).
The FiTNEss trial is designed as an all-comers study with few exclusion criteria other than necessary for safety including some haematological and biochemical parameters, but there is no exclusion based on renal function. Patients with grade 2 or greater baseline peripheral neuropathy, current systemic infection or recent surgery or other cancer are excluded. Here we report the demographics for the first patients recruited, including IMWG frailty assessments and MRP to demonstrate the feasibility of recruiting frail patients to randomised phase III clinical trials.
Results
The FiTNEss trial opened on 04/08/2020 during the second wave of the COVID-19 pandemic in the UK. At the time of data cut off (14/07/2021) recruitment is active at 84 sites, with 180 patients randomised.
Baseline characteristics for the randomised patients are shown in Figure 1B. The median age of patients is 77 years (range 64, 93) with 36.1% aged 76-80 and 26.1% over 80. In keeping with the older patient population 26.6% have an ECOG performance status of 2 or 3 and 31.7% ISS stage III. The IMWG frailty classification at baseline is FIT 43/180 (23.9%), UNFIT 53/180 (29.4%) and FRAIL 84/180 (46.7%).
The effect of using age groups on the definition of patient frailty was explored. The IMWG frailty score defines all patients over 80 as FRAIL whilst an age of 76-80 contributes one point to the score. An analysis of patients' frailty was repeated with the contribution of age removed. For those aged over 80 years (n=47, 100% FRAIL) we found that 20 (42.6%) would have been re-classified as FIT and 18 (38.3%) as UNFIT, with only 9 (19.2%) retaining the FRAIL category. For those aged 76-80 (n=65, 53.8% UNFIT, 46.2% FRAIL) all 35 patients previously classified as UNFIT became FIT (53.8%) whilst 19 (29.2%) classed as FRAIL became UNFIT with 11 (16.9%) remaining FRAIL.
The MRP classification, using age as a continuous variable, was Low-risk 45/180 (25.0%), Medium-risk 46/180 (25.6%), High-risk 75/180 (41.7%) and not available for 14/180 (7.8%) patients. Concordance between the IMWG frailty score and the MRP occurred in 48.9% of patients (88/180). 37.2% of FIT patients were classified as MRP Low-risk, 32.1% of UNFIT patients as MRP Medium-risk and 65.5% of FRAIL patients as MRP High-risk.
Discussion
The FiTNEss trial demonstrates the feasibility of recruiting older, less fit patients to clinical trials. Recruitment of patients classified as FRAIL was very high despite the COVID pandemic, likely due to the all-oral nature of the regimen under investigation enabling patients to avoid attendance at hospital day units for treatment and associated exposure risk. In the population recruited to date we found age to be a key contributor to the FRAIL category of the IMWG frailty score. Concordance between IMWG frailty score and MRP was highest in FRAIL/High-risk patients. The first interim analysis of the primary objectives is planned when 50% of required participants for R1 have reached 60 days post R1, which is anticipated in Q2 of 2022.
Display omitted
Cook: Amgen: Consultancy, Honoraria, Research Funding; BMS: Consultancy, Honoraria, Research Funding; Sanofi: Consultancy, Honoraria; Karyopharm: Consultancy, Honoraria; Roche: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria; Oncopeptides: Consultancy, Honoraria; Takeda: Consultancy, Honoraria, Research Funding; Janssen: Consultancy, Honoraria, Research Funding. Pawlyn: Sanofi: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene / BMS: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Honoraria. Royle: BMS: Research Funding; Merck Sharpe and Dohme: Research Funding; Amgen: Research Funding; Takeda: Research Funding. Coulson: BMS / Celgene: Honoraria; Merck Sharpe and Dohme: Research Funding; Amgen: Research Funding; Takeda: Research Funding. Jenner: BMS/Celgene: Consultancy, Honoraria, Speakers Bureau; Janssen: Consultancy, Honoraria, Speakers Bureau; Pfizer: Consultancy; Takeda: Consultancy. Kishore: Sanofi: Other: Attending fees; Celgene: Other: Attending fees; Takeda: Other: Attending fees; Jannsen: Other: Attending fees. Rabin: BMS / Celgene: Consultancy, Honoraria, Other: Travel support for meetings; Takeda: Consultancy, Honoraria, Other: Travel support for meetings; Janssen: Consultancy, Honoraria, Other: Travel support for meetings. Best: BMS/Celgene: Research Funding; Merck Sharpe and Dohme: Research Funding; Amgen: Research Funding; Takeda: Research Funding. Gillson: BMS / Celgene: Research Funding; Meck Sharpe and Dohme: Research Funding; Amgen: Research Funding; Takeda: Research Funding. Henderson: Takeda: Research Funding; Amgen: Research Funding; Merck Sharpe and Dohme: Research Funding; BMS / Celgene: Research Funding. Olivier: Merck Sharpe and Dohme: Research Funding; Takeda: Research Funding; Amgen: Research Funding; Celgene / BMS: Research Funding. Kaiser: AbbVie: Consultancy; GSK: Consultancy; Karyopharm: Consultancy, Research Funding; Pfizer: Consultancy; Amgen: Honoraria; Seattle Genetics: Consultancy; Takeda: Consultancy, Other: Educational support; Janssen: Consultancy, Other: Educational support, Research Funding; BMS/Celgene: Consultancy, Other: Travel support, Research Funding. Drayson: Abingdon Health: Current holder of individual stocks in a privately-held company. Jones: Janssen: Honoraria; BMS/Celgene: Other: Conference fees. Cairns: Merck Sharpe and Dohme: Research Funding; Amgen: Research Funding; Takeda: Research Funding; Celgene / BMS: Other: travel support, Research Funding. Jackson: celgene BMS: Consultancy, Honoraria, Research Funding, Speakers Bureau; amgen: Consultancy, Honoraria, Speakers Bureau; takeda: Consultancy, Honoraria, Research Funding, Speakers Bureau; GSK: Consultancy, Honoraria, Speakers Bureau; J and J: Consultancy, Honoraria, Speakers Bureau; oncopeptides: Consultancy; Sanofi: Honoraria, Speakers Bureau.
Frailty-score adapted dosing strategies
Introduction: Daratumumab in combination with bortezomib and dexamethasone (DVd) demonstrated a superior overall response rates (ORR) and progression free survival (PFS) compared to Vd in the CASTOR ...phase 3 trial for patients with RRMM. On this basis, DVd was recommended in March 2019 for UK patients with RRMM that had 1 prior line (PL). Discrepancies in outcomes between patients treated in clinical trials compared to routine practice is well recognised due to a combination of patient, disease and treatment-related factors. In addition, bortezomib is often administered once-weekly in routine practice to minimise neuropathy, while CASTOR used bi-weekly bortezomib dosing. As a result, the real-world outcomes of patients treated with DVd are yet to be determined.
The primary aims of this analysis was to assess the ORR and PFS for patients with RRMM with 1PL treated with DVd in routine practice. Secondary aims were to assess OS, time to next treatment (TTNT), and efficacy in different sub-groups (high risk cytogenetics, previous proteasome inhibitor (PI) exposure, refractoriness of prior therapies, bi-weekly vs weekly bortezomib schedule, and previous treatment free interval (TFI)).
Methods: This was a retrospective analysis from 14 centres (academic and community hospitals; 7 within the West Midlands Research Consortium (WMRC)) treated with DVd between March 2019 and June 2021. Patients received daratumumab (IV and then SC from June 2020) weekly in cycles 1-3, on day 1 of a 3-week cycle during cycles 4-8, and then monthly from cycle 9 to progression. SC Bortezomib was predominantly given weekly for cycles 1-8 although 5 centres used bi-weekly dosing for selected patients with aggressive disease. Adverse events were graded as per CTCAE criteria.
Results: 288 patients were included, with a median age of 69 years (range 20-88) (Table 1). Patients received a median of 1 PL (range 1-2) with 93% (269) 1PL, 7% (18) 2 PL (due to COVID-19 measures). The majority had an ECOG performance status of 0-2 (98%) and most received weekly bortezomib (n=201). This population differed from those with 1PL treated on CASTOR in being older, more were ISS 3 (31% vs 19%, p=0.0145), and more had prior bortezomib exposure (71% vs 51%, p=0.0003), 4% were PI refractory, 9% had a GFR of <30ml/min (<20ml/min was an exclusion from CASTOR), and 2% had an ECOG performance status of ≥3.
The ORR was 76%, with >VGPR in 54% (Table 2), with no significant difference in response between patients receiving biweekly vs weekly bortezomib (85% vs 83%; p=0.71). The median time to response was 1.6m.
With a median follow up of 15m, the median PFS was 14m (95% CI 11.6-16). High cytogenetic risk patients had inferior outcomes: median PFS 10m (95% CI 6-14) for high risk vs not reached for standard risk (p=0.043); as did those with advanced ISS: median PFS was not reached, 15 and 12m for stage I, II and III respectively (p=0.05). For 15 patients with extramedullary disease (EMD), the median PFS was 3m (95% CI 1-5). Median PFS for patients who were PI refractory was shorter (10m vs 15m for PI sensitive patients (p=0.006)). There was no difference in median PFS for patients with prior PI exposure vs no prior PI (15 vs 13m; p=0.75), or according to weekly or bi-weekly bortezomib schedule (11 vs 15m; p=0.14). The median TTNT was 21m (95% CI 17-25). Overall, the median duration of treatment was 8m and 25 patients (9%) stopped treatment to receive a second autologous stem cell transplant. Those that had a prior TFI of >12m had a longer median PFS of 21m vs 10m (p=0.0004). The median OS has not been reached, with an estimated 2-year OS of 74%. For patients with high risk cytogenetics the median OS was 16m (95% CI 9-23; vs not reached for standard risk; p=0.0006), with estimated 2-year OS in the high risk group of 36%. There was no difference in OS for patients treated with biweekly vs weekly bortezomib (not reached for either; p=0.38).
DVd was generally well tolerated with 6% stopping due to adverse events (CASTOR 9.5%). Grade 3 or 4 toxicity occurred in 62 (22%) most commonly neutropenia and thrombocytopenia, with any grade infusion reactions reported in 27 (9%).
Conclusions: These real-world data of DVd at 1 st relapse demonstrated good tolerability and high response rates with a weekly bortezomib schedule despite a more heterogenous population. However, high risk patients by cytogenetics, ISS or EMD had inferior outcomes as did those treated within 12 months from first line treatment.
Display omitted
Cook: Karyopharm: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria; Sanofi: Consultancy, Honoraria; Takeda: Consultancy, Honoraria, Research Funding; Amgen: Consultancy, Honoraria, Research Funding; BMS: Consultancy, Honoraria, Research Funding; Oncopeptides: Consultancy, Honoraria; Roche: Consultancy, Honoraria; Janssen: Consultancy, Honoraria, Research Funding. Pratt: Binding Site: Consultancy; BMS/Celgene: Consultancy; Gilead: Consultancy; Janssen: Consultancy; Takeda: Consultancy; Amgen: Consultancy. Kishore: Celgene: Other: Attending fees; Jannsen: Other: Attending fees; Sanofi: Other: Attending fees; Takeda: Other: Attending fees. Yong: Amgen: Honoraria; Autolus: Research Funding; BMS: Research Funding; Janssen: Honoraria, Research Funding; Sanofi: Honoraria, Research Funding; GSK: Honoraria; Takeda: Honoraria. Popat: Abbvie, Takeda, Janssen, and Celgene: Consultancy; Takeda: Honoraria, Other: TRAVEL, ACCOMMODATIONS, EXPENSES; GlaxoSmithKline: Consultancy, Honoraria, Research Funding; AbbVie, BMS, Janssen, Oncopeptides, and Amgen: Honoraria; Janssen and BMS: Other: travel expenses.
Summary
Second‐generation immunomodulatory agents, such as lenalidomide, have a more favourable side‐effect profile than the first‐generation thalidomide, but their optimum combination and duration ...for patients with newly diagnosed transplant‐ineligible myeloma (ND‐TNE‐MM) has not been defined. The most appropriate delivery and dosing regimens of these therapies for patients at advanced age and frailty status is also unclear. The Myeloma XI study compared cyclophosphamide, thalidomide and dexamethasone (CTDa) to cyclophosphamide, lenalidomide and dexamethasone (CRDa) as induction therapy, followed by a maintenance randomisation between ongoing therapy with lenalidomide or observation for patients with ND‐TNE‐MM. CRDa deepened response but did not improve progression‐free (PFS) or overall survival (OS) compared to CTDa. However, analysis by age group highlighted significant differences in tolerability in older, frailer patients that may have limited treatment delivery and impacted outcome. Deeper responses and PFS and OS benefits with CRDa over CTDs were seen in patients aged ≤70 years, with an increase in toxicity and discontinuation observed in older patients. Our results highlight the importance of considering age and frailty in the approach to therapy for patients with ND‐TNE‐MM, highlighting the need for prospective validation of frailty adapted therapy approaches, which may improve outcomes by tailoring treatment to the individual.
Introduction:
Systemic AL amyloidosis is a rare multisystem disease caused by an underlying plasma cell dyscrasia with amyloid fibril deposition causing progressive organ failure. Treatment of the ...underlying plasma cell disorder underpins the management of AL amyloidosis with bortezomib-based regimes as standard first line treatment. Thalidomide has activity in AL amyloidosis used in low doses in combination with cyclophosphamide and dexamethasone. Carfilzomib (Kyprolis), a second generation irreversible inhibitor of the proteasome, is licenced for treatment of relapsed refractory myeloma. This prospective phase 1 multicentre study was designed to define the maximum tolerated dose (MTD) and recommended dose (RD) of one weekly dose of carfilzomib in combination with a fixed dose of thalidomide and dexamethasone (KTD) in patients with relapsed refractory amyloidosis.
Methods and Patients
Patients were recruited for treatment with carfilzomib in escalating dose cohorts using a 3+3 dose escalation design at three planned dose levels (Table 1) - all participants received carfilzomib 20mg/m2 on cycle 1 day 1. The primary endpoint was to define the MTD, RD and assess the safety and tolerability of KTD. The key secondary endpoint was a preliminary assessment of the activity of KTD.
Results
A total of 10 patients were recruited (6 male, 4 female) with a median age of 64 years (30% >70 years). The mean time from AL amyloidosis diagnosis for Dose levels 0 and 1 was 7.8 years (SD ±3.87 yrs.) and 3.2 years (SD ± 1.80) respectively. All non-refractory patients had received at least two previous lines of therapy, with a maximum of four previous lines of therapy. The median creatinine was 77.0µmol/L, the median NT-proBNP was 53.3pmol/L and dFLC at the time of treatment was 77.0mg/L.
Three evaluable patients were recruited to Dose Level 0 with no dose limiting toxicities (DLTs) observed. A further 3 evaluable patients were recruited to Dose Level 1 - one patient experienced a DLT (acute kidney injury). Hence, 3 further patients were recruited at this dose level. One participant had a serious adverse event (SAE) following day 1 dosing at 20mg/m2 - deemed not evaluable for DLT assessment as received no further treatment. Three further patients were recruited at Dose level 1 with no further DLT's. The data monitoring committee decided that it was not in the patients' best interest to proceed to Dose level 2, as significant evidence of activity at dose level 1 and concern about potential toxicity.
As of June 2019, 7 participants have completed 3 cycles and 4 participants (40%) have completed 6 cycles. Responses were determined centrally according to amyloidosis consensus criteria 2005. The overall hematologic response rate at end of 3 cycles was 70%. This included: complete response - 1 (10%); very good partial response - 3 (30%) and partial response 3 (30%). Of the 3 participants at Dose level 1, 1 participant had a VGPR, 1 had PR and 1 had no response (discontinued at the end of cycle 2). One patient had no response by the end of cycle 2 (discontinued due to toxicity) and 2 patients with DLT's were not assessable for response.
A total of 3 participants had SAE's: 1. At dose level 1, grade 3 acute kidney injury which was deemed to be DLT, which recovered with supportive care. 2. At dose level 1, pyrexia, hypotension and hypoxia requiring intensive care admission after day 1 dose of 20mg/m2. There was no clear evidence of infection and this was deemed to be a SAE due to carfilzomib (but not DLT). 3. At dose level 1, grade 3 abdominal pain deemed unrelated to study medication. There were 66 other grade 1 or 2 adverse events reported from 9 participants from the first 3 cycles. There were no SUSARs or deaths in the study reported to date. None of the patients had worsening cardiac function. Results here are preliminary with further endpoints and detail to be presented when all participants have completed therapy.
Conclusion
This study defined, in combination with thalidomide and dexamethasone, the recommended dose of carfilzomib was 45mg/m2 on days 1, 8 and 15. The MTD of carfilzomib was not reached. Three participants experienced a SAE and a number of participants had grade 1-2 AE's. At the end of 3 cycles, 70% of participants achieved a hematologic response with 40% VGPR or better which appears comparable to other studies in relapsed AL amyloidosis. KTD is a potentially effective regime that can be considered for further study in relapsed refractory systemic AL amyloidosis.
Display omitted
Garg:Novartis: Consultancy, Honoraria. Hall:Celgene, Amgen, Janssen, Karyopharm: Other: Research funding to Institution. Jenner:Abbvie, Amgen, Celgene, Novartis, Janssen, Sanofi Genzyme, Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Kishore:Celgene, Jazz, Takeda: Other: Travel expenses; Celgene, Takeda, Janssen: Honoraria, Speakers Bureau. Pitchford:Amgen: Other: Research funding to institution. Flanagan:Amgen, Celgene, Janssen, Karyopharm: Other: Research funding to Institution. Oughton:Amgen: Other: Research funding to institution. Brown:Amgen, Celgene, Janssen, Karyopharm: Other: Research funding to Institution. Wechalekar:Amgen: Research Funding; GSK: Honoraria; Takeda: Honoraria; Celgene: Honoraria; Janssen-Cilag: Honoraria.
PDF
