Open-label Expanded Access Program Research Articles

Avelumab first-line maintenance treatment in patients with locally advanced or metastatic urothelial carcinoma: real-world results from a Korean expanded access program.

The JAVELIN Bladder 100 phase 3 trial demonstrated the efficacy and safety of avelumab administered as first-line (1L) maintenance treatment in patients with advanced urothelial carcinoma (UC) without disease progression after 1L platinum-based chemotherapy. This study provides the first real-world data from Korea regarding avelumab 1L maintenance treatment, comprising data obtained from a nationwide expanded access program (EAP). This open-label EAP was conducted at five centers from September 2021 until June 2023. Eligible patients had unresectable locally advanced or metastatic UC and were progression free after 1L platinum-based chemotherapy. Patients received avelumab 10 mg/kg intravenously every 2 weeks per local prescribing information. Safety and effectiveness were assessed by treating physicians according to routine practice. Overall, 30 patients were enrolled. At initial UC diagnosis, 20 patients (66.7%) had stage 4 disease and 12 (40.0%) had visceral metastases. The most common 1L chemotherapy regimen was gemcitabine + cisplatin (21 patients; 70.0%). All but one patient (96.7%) had received 4-6 cycles of 1L chemotherapy. The median interval from end of 1L chemotherapy to start of avelumab was 4.4 weeks. Median duration of avelumab treatment was 6.2 months (range, 0.9-20.7); nine patients (30.0%) received >12 months of treatment. Adverse events related to avelumab occurred in 21 patients (70.0%) and were grade ≥3 or classified as serious in three patients (10.0%). Median progression-free survival was 7.9 months (95% CI, 4.3-13.1). Overall survival was not analyzed because only one patient died. Results from this EAP demonstrated the clinical activity and acceptable safety of avelumab 1L maintenance treatment in Korean patients with advanced UC, consistent with previous studies.

Omidubicel-Onlv for Allogeneic Transplantation (allo-HCT) in Patients with Hematologic Malignancies: Results of a Multicenter Open Label Expanded Access Program

Introduction Omidubicel-onlv is a nicotinamide-modified allogeneic hematopoietic progenitor cell therapy donor source derived from umbilical cord blood (UCB). A phase 3 randomized study (NCT02730299) demonstrated improved hematopoietic recovery and decreased infections in patients transplanted with omidubicel compared to UCB. An expanded access program (EAP) was conducted to provide access to omidubicel in advance of commercial availability in the United States (US) in April 2023. Objective This was an open-label, single-arm EAP evaluating clinical outcomes in patients with hematologic malignancies following allo-HCT with omidubicel. Methods Eligible patients (≥12 years) with hematologic malignancies received myeloablative conditioning, prophylactic medications, and supportive care as per institutional guidelines. Patients were monitored for neutrophil and platelet engraftment, infections, graft versus host disease (GVHD), and additional clinical events for up to 2 years post-transplantation. Results were retrospectively compared with previously described outcomes in patients from the phase 3 study comparing transplant with omidubicel (P3-OMI, n=52) and unmanipulated UCB (P3-UCB, n=56). Results Between July 2020 and April 2023, 36 patients were enrolled and 29 (18 males, 11 females) were transplanted at 5 US sites. Median age was 39 years (range: 20-73); 55% were White, 21% Asian, 17% Black, and 7% other. Diagnoses were acute myelogenous leukemia (38%), acute lymphocytic leukemia (28%), myelodysplastic syndrome (21%), and other (14%). All patients received myeloablative conditioning (total body irradiation-based: 58.5%, chemotherapy alone: 34.5%). Median transplanted CD34+ cell dose was 5.6x10 6 cells/kg (range: 1.8-18.7x10 6 cells/kg) and HLA match was 4/6 in 52%, 5/6 in 45%, and 6/6 in 3%. Median follow-up was 6.3 months (range: 0.3-27.7). No infusion reactions were reported. Median time to neutrophil (≥500/µl x3 days) and platelet (>20,000/µl x3 days) engraftment were 13 and 34 days, respectively. Primary graft failure occurred in 2 (6.9%) patients, both alive >100 days after second haploidentical transplant. The incidences of first grade 2-3 bacterial and invasive (grade 3) fungal infection through 100 days post-transplant were 16.9% and 0%, respectively. The incidence of grade 3 viral infections 1-year post-transplant was 13.4%. At 100 and 365 days post-transplant, disease-free survival (DFS) rates were 95.2% and 82.5%, and overall survival (OS) rates were 96.3% and 84.2%, respectively. Acute GVHD was reported in 13 (44.8%) patients (grade 2: 34.5%, grade 3: 10.3%) and mild chronic GVHD in 1 (3.5%) patient. There were 4 deaths (13.8%): 2 due to relapse (Days 275 and 381), 1 due to infection (Day 135) and 1 due to respiratory failure (Day 10). Post-transplant lymphoproliferative disease was reported in 1 patient. Demographic and disease characteristics were similar to those in the phase 3 omidubicel registration trial, including racial and ethnic diversity (>39% minorities). Neutrophil engraftment time in EAP patients was similar to P3-OMI (10 days) and shorter than P3-UCB (20.5 days). Similarly, median platelet recovery was similar to P3-OMI (37 days) and shorter than P3-UCB (50 days). Infection, GVHD, DFS, and OS in EAP were also similar to those observed in P3-OMI (Table 1). Conclusion In a real-world EAP setting, the outcomes of allo-HCT with omidubicel in patients with hematologic malignancies were consistent with those from the phase 3 registration study. These data support the role of omidubicel as a donor source, particularly for patients from diverse racial backgrounds.

Final analysis of potential drug-drug interactions between highly purified cannabidiol and anti-seizure medications in an open-label expanded access program.

The aim of this study was to assess potential drug-drug interactions between highly purified cannabidiol (CBD) and anti-seizure medications (ASMs). Our group previously reported that in a sample of adults and children receiving CBD in an open-label expanded access program, there were several ASMs noted to increase in serum levels with increasing doses of CBD. We analyzed if an increased number of observations over time resulted in changes in potential interactions and if potential interactions were associated with time since enrollment, demographics, or the overall rating of adverse effects. In 169 participants (80 adults), with increasing weight-based CBD dose, there were associated increases in serum levels of clobazam and N-desmethylclobazam, free valproate, felbamate, and topiramate in the adult and pediatric arms combined, levetiracetam in the pediatric arm only, and permapanel in the adult arm only. There were no associations noted in these level changes with time since enrollment, biological sex, and adverse events profile scores. This study confirms some previously identified interactions with CBD and identifies other potential pharmacokinetic interactions; however, the clinical significance of these observations is likely minor, and there is no effect of time on these findings.

An open-label expanded access program of afatinib in EGFR tyrosine kinase inhibitor-na\xefve patients with locally advanced or metastatic non-small cell lung cancer harboring EGFR mutations

BackgroundAfatinib is approved globally for EGFR-TKI treatment-naïve patients with EGFR mutation-positive non-small cell lung cancer (NSCLC). In this Korean expanded access program, we evaluated its ‘real-world’ safety and efficacy.MethodsEGFR-TKI treatment-naïve patients with EGFR mutation-positive NSCLC received afatinib 40 mg/day until disease progression or other withdrawal criteria. Dose reductions were permitted for adverse events (AEs). The primary endpoint was the number of patients with AEs (CTCAE version 3.0). Other endpoints included progression-free survival (PFS), overall response rate (ORR), duration of response (DOR), and changes in investigator-assessed cancer-related symptoms.ResultsEighty-eight patients received afatinib, including 27 (31%) with brain metastases and 16 (18%) with uncommon EGFR mutations. Median PFS was 17.0 months (95% confidence interval [CI] 12.9–23.3 months). Grade 3 treatment-related AEs (TRAEs) were reported in 51 (58%) patients; the most common were diarrhea (22%) and rash/acne (20%). No grade > 3 TRAEs were reported. AEs leading to dose reduction occurred in 49 (56%) patients. Treatment discontinuation due to TRAEs occurred in 4 (5%) patients. ORR was 81% overall, 89% in patients with brain metastases, and 55% in patients with uncommon mutations (excluding T790M/exon 20 insertions). Median DOR was 15.1 months (95% CI 12.4–21.4 months). Cancer-related symptoms were improved/unchanged/worsened in 34–66%/36–66%/0–3% of patients over the first year.ConclusionsNo unexpected safety signals for afatinib were observed. AEs were manageable; the treatment discontinuation rate was low. Afatinib showed encouraging efficacy in a broad patient population including those with brain metastases or tumors harboring uncommon EGFR mutations.Trials registrationClinicalTrials.gov NCT01931306; 29/08/2013.

The long-term efficacy of cannabidiol in the treatment of refractory epilepsy.

Cannabidiol (CBD) has been shown to reduce seizures among patients with refractory epilepsies of various etiologies in recent clinical trials and an expanded access program (EAP). Most studies report efficacy over short time periods (<1year), with little published on longer term efficacy. Here, we investigate the efficacy of CBD for a treatment period of up to 60months (median = 45.5months). We conducted a retrospective review of patient-reported seizure logs and medical records for 54 subjects with refractory epilepsy who enrolled in the Massachusetts General Hospital's open-label EAP for CBD as a new treatment for epilepsy. We analyzed the effect of CBD on seizure frequencies and concomitant antiepileptic drug (AED) use at 1year after starting treatment and the most recent study visit. Our results indicate that CBD maintains its efficacy for controlling seizures from Year 1 to the most recent study visit. The percentage of seizure responders remained similar at these time points (41.7%-42.6%), and the seizure response rate was also maintained (p=.12). Efficacy was also seen over a broad dose range, and up to 50mg/kg/day. CBD was particularly effective for controlling seizures in the setting of tuberous sclerosis complex and for reducing epileptic spasms and absence seizures. Although CBD use did not lead to an overall decrease in concomitant AEDs, most subjects reduced the dose of at least one concomitant AED compared to baseline. CBD was generally well tolerated, with drowsiness and diarrhea as the primary adverse reactions. This study demonstrates CBD does not lose its efficacy in controlling seizures over a treatment period of up to 60months. Taken alongside other results on the efficacy and tolerability of CBD in the treatment of refractory epilepsies, our results provide evidence that CBD is an effective, safe, and well-tolerated AED for long-term use.

Drug–drug interactions with cannabidiol (CBD) appear to have no effect on treatment response in an open-label Expanded Access Program

ObjectiveWe have previously shown that cannabidiol (CBD; Epidiolex®) significantly affects levels of clobazam/N-desmethylclobazam, rufinamide, topiramate, zonisamide, and eslicarbazepine. In the present study, we tested whether the presence of concomitant clobazam affected seizure frequency and severity (treatment response) 12 weeks after initiation of therapy with CBD in patients with treatment-resistant epilepsy (TRE). The secondary questions were whether the presence of any of the other antiepileptic drugs (AEDs) had an effect on seizure frequency or severity at 12, 24, or 48 weeks after therapy initiation. MethodsOne hundred and thirty-two adults and children with TRE receiving CBD were studied prospectively. Participants were separated into two groups — either taking (CBD + clobazam) or not taking concomitant clobazam (CBD − clobazam). In the secondary analyses, participants were divided into groups depending on whether they were taking at least 1/4 of the other AEDs shown to interact with CBD (iAED). Seizure counts and Chalfont Seizure Severity Scale (CSSS) were obtained at baseline, 12, 24, and 48 weeks. Groups were compared at each respective time point in the study using generalized estimating equations (GEE) analyses. ResultsAll groups demonstrated statistically significant reductions in seizure frequency and severity from baseline (all P < 0.05). When participants on CBD + clobazam were compared with CBD − clobazam, there were no significant differences in seizure frequency and severity reduction between the groups at 12 weeks (both P > 0.05). When comparing groups with iAEDs vs. group without iAEDs, independent of coadministration of clobazam, no differences in treatment response were observed (all P > 0.05). Longitudinal analyses up to 48 weeks after therapy initiation did not reveal any differences in treatment response between groups. ConclusionThese analyses suggest that concomitant to CBD, AEDs may not have an effect on reducing seizure frequency and severity in patients with TRE.

Safety of trifluridine/tipiracil (FTD/TPI) in elderly patients with metastatic colorectal cancer.

752 Background: Elderly patients (≥65 yrs) with metastatic colorectal cancer (mCRC) are more likely to have comorbid conditions than younger patients ( &lt; 65 yrs), limiting their therapeutic options. As previously reported (Mayer et al. J Clin Oncol 2017;35:abs 3559), FTD/TPI confirmed its clinical profile in mCRC in a real-world setting. Here, we report the safety and tolerability profile of FTD/TPI from the expanded-access program (EAP) in patients aged ≥65 yrs. Methods: Patients (≥18 yrs) with mCRC following ≥2 regimens of anticancer therapy and an Eastern Cooperative Oncology Group performance status of 0 or 1 were enrolled to this open-label EAP. Patients received FTD/TPI 35 mg/m2 twice daily for 5 days followed by 2 days’ rest for 2 weeks, with a 14-day rest period (28-day treatment cycle). Data were collected for therapy duration, treatment discontinuation, and adverse events (AEs). Results: Of 549 patients, 377 (68.7%) were aged &lt; 65 and 172 (31.3%) were ≥65. The treatment duration of FTD/TPI was similar between &lt; 65 and ≥65 yrs (Table). A lower proportion of those aged ≥65 had fatigue and nausea compared with &lt; 65 (Table). However, the frequency of neutropenia and diarrhea was slightly increased in those ≥65 compared with &lt; 65 (Table). One patient (0.6%) in the ≥65 group developed febrile neutropenia compared with 9 (2.4%) in the &lt; 65 group, with no associated deaths in either group. Conclusions: This analysis from the EAP showed that the safety profile and treatment duration of FTD/TPI in patients aged ≥65 with mCRC were similar to those in patients aged &lt; 65. FTD/TPI is well tolerated and can be considered in patients aged ≥65 with mCRC. Clinical trial information: NCT-02286492. [Table: see text]

Sorafenib-Regorafenib Sequential Therapy in Advanced Hepatocellular Carcinoma: A Single-Institute Experience

Objectives: Previously, no therapeutic agent has been known to improve the overall survival compared with placebo in patients with hepatocellular carcinoma (HCC), who have progressed after sorafenib. In this patient population, regorafenib was first demonstrated to confer a survival benefit in the RESORCE trial, and subsequently it was approved as a second-line treatment for patients with advanced HCC. An open-label expanded access program (EAP) of regorafenib was implemented for compassionate use. We investigated the efficacy and safety of regorafenib based on our experience of the RESORCE trial and the EAP. Methods: Data from 5 patients from the RESORCE trial and 6 from the EAP were analyzed retrospectively. All patients had tolerated prior sorafenib and were progressing during sorafenib treatment. Results: The median progression-free survival was 9.2 months (95% CI 2.3-16.1). One patient achieved a partial response and 7 achieved stable disease. The objective response rate was 9.1%, and the disease control rate was 72.7%. No treatment-associated mortalities were observed. Grade 3 hypophosphatemia was observed in 2 patients, grade 2 anorexia was observed in 5 patients, and grade 3 neutropenia was observed in 2 patients. Grade 2 and grade 3 thrombocytopenia were observed in 2 and 3 patients, respectively. All treatment-related adverse events were improved by reduction or interruption of regorafenib. Five patients showed decreased serum albumin levels. Conclusion: Sorafenib and regorafenib sequential therapy presents a safe and effective treatment option for patients with advanced HCC.

Safety of trifluridine/tipiracil for metastatic colorectal cancer in African American patients participating in an expanded access program.

e15039 Background: A Phase 3 clinical trial (RECOURSE) showed that trifluridine/tipiracil (FTD/TPI) was effective in the treatment of refractory metastatic colorectal cancer (mCRC) (Mayer et al. NEJM 2015;372:1909-19). An expanded-access program (EAP) for patients with refractory mCRC assessed FTD/TPI safety in a real-world setting. One limitation of RECOURSE was the small number of African-American (AA) patients enrolled in the study (n=8). The EAP enrolled 45 AA patients, enabling assessment of FTD/TPI safety in this population. Methods: Patients aged ≥18 years with refractory mCRC resistant to ≥2 regimens of standard chemotherapy and an ECOG performance status of 0 or 1 were enrolled in this open-label EAP. Patients received FTD/TPI 35 mg/m2 twice daily for 5 days followed by 2 days’ rest repeated twice followed by 14 days’ rest over a 28-day treatment cycle until drug discontinuation. We investigated duration of exposure to FTD/TPI and associated adverse events (AEs) in AA patients to compare them with non-AA and US patients from RECOURSE. Results: Median duration of FTD/TPI therapy for AA patients in the EAP was 9.7 weeks, similar to non-AA patients in the EAP (9.7 weeks) and US patients in RECOURSE (8.9 weeks) (differences not statistically significant). 73.3% of AA patients (n=33) in the EAP discontinued treatment due to disease progression and 8.9% (n=4) discontinued due to AEs. AEs related to FTD/TPI are summarized in the table. Conclusions: Lung cancer patients in Eastern North Carolina possess a strikingly poor inflammatory signature with significant implications for quality of life and survival. Clinical trial information: NCT02286492. [Table: see text]

An open-label expanded-access study of trifluridine/tipiracil for metastatic colorectal cancer.

3559 Background: A Phase 3 clinical trial (RECOURSE) showed that trifluridine/tipiracil (FTD/TPI) was effective in the treatment of refractory metastatic colorectal cancer (mCRC) treated with standard chemotherapy and targeted-therapy drugs (Mayer et al. N Engl J Med 2015;372:1909-19). An expanded-access program (EAP) was started to provide access to FTD/TPI for patients with mCRC with similar eligibility and to further assess the safety of FTD/TPI in a “real-world” setting in US patients. Methods: Patients aged ≥18 years with refractory mCRC resistant to ≥2 regimens of standard chemotherapy with appropriate biologics and an Eastern Cooperative Oncology Group performance status of 0 or 1 were enrolled to this open-label EAP. Patients received FTD/TPI 35 mg/m2twice daily for 5 days followed by 2 days’ rest repeated twice followed by 14 days’ rest over a 28-day treatment cycle until drug discontinuation. Sites reported duration of therapy, discontinuation due to disease progression, and adverse events (AEs) for each patient. Results: 549 patients were enrolled; 53.2% were male. Median duration of FTD/TPI therapy was 9.7 weeks, which was similar to US patients from RECOURSE (8.9). 10.2% of patients died during the study period, 9.7% due to disease progression. 76.1% of patients discontinued treatment due to disease progression and 4% discontinued due to AEs. Drug-related clinically significant AEs (all grades) are summarized in the table. Conclusions: Patients with refractory mCRC in this EAP had a similar exposure duration to that reported in US patients from RECOURSE, with no unexpected safety concerns. While gastrointestinal toxicity was lower in this population, this may be due to reporting of “significant” events. The clinical profile of FTD/TPI is confirmed in this larger, non-randomized “real-world” experience. Sponsorship: Taiho Oncology, Inc. Editorial Assistance: Complete HealthVizion. Clinical trial information: NCT02286492. [Table: see text]

Safety and efficacy results of the advanced renal cell carcinoma sorafenib expanded access program in North America

The Advanced Renal Cell Carcinoma Sorafenib (ARCCS) program made sorafenib available to patients with advanced renal cell carcinoma (RCC) before regulatory approval. In this nonrandomized, open-label expanded access program, 2504 patients from the United States and Canada were treated with oral sorafenib 400 mg twice daily. Safety and efficacy were explored overall and in subgroups of patients including those with no prior therapy, nonclear cell (nonclear cell) RCC, brain metastases, prior bevacizumab treatment, and elderly patients. Sorafenib was approved for RCC 6 months after study initiation, at which time patients with no prior therapy or with nonclear cell RCC could enroll in an extension protocol for continued assessment for a period of 6 months. The most common grade > or =2 drug-related adverse events were hand-foot skin reaction (18%), rash (14%), hypertension (12%), and fatigue (11%). In the 1891 patients evaluable for response, complete response was observed in 1 patient, partial response in 67 patients (4%), and stable disease for at least 8 weeks in 1511 patients (80%). Median progression-free survival in the extension population was 36 weeks (95% confidence interval [CI], 33-45 weeks; censorship rate, 56%); median overall survival in the entire population was 50 weeks (95% CI, 46-52 weeks; censorship rate, 63%). The efficacy and safety results were similar across the subgroups. Sorafenib 400 mg twice daily demonstrated activity and a clinically acceptable toxicity profile in all patient subsets enrolled in the ARCCS expanded access program (clinicaltrials.gov identifier: NCT00111020).

The Impact of Cytogenetics on the Outcomes of Treatment with Lenalidomide Plus Dexamethasone in Relapsed or Refractory Multiple Myeloma.

Background: Lenalidomide improves survival for patients with relapsed or refractory multiple myeloma (MM). However, the benefit of this treatment in patients with highrisk cytogenetic abnormalities is not well studied. We have previously reported in an initial sub-analysis of a large, open-label study (MM016 study) the effects of the most common unfavorable cytogenetic abnormalities on outcomes in MM patients treated with lenalidomide plus dexamethasone. Since then we have performed an update of this sub-analysis within a larger cohort of patients and a longer median follow-up time of 19.6 months.Methods: The MM016 is a multicenter single arm open label expanded access program for Lenalidomide in relapsed and refractory MM. Patients received dexamethasone orally (40mg, days 1–4; 9–12 and 17–20 for 4 cycles, then days 1–4 beginning with cycle 5) and Lenalidomide 25mg orally on days 1–21 of a 28 days cycle. Using fluorescence in situ hybridization, we examined the influence of three most common and recurrent cytogenetic abnormalities [del(13q), t(4;14), and del(17p13)] in 130 patients with FISH results available for the three genomic aberrations. Blade criteria were used to define RR. TTP and OS were defined according to the international uniform response criteria.Results: The median age was 61 yrs (31–84), 55.4% had ISS stage II or III, median beta2-microglobulin was 3.125 mg/L (1.1–16.75), median number of prior treatments was 2 (1–6) with 53.8% previously treated with thalidomide, 45.9% with bortezomib and 73.3% with SCT. Del(13q), t(4;14) and del(17p13) were detected in 54 (41.5%), 28(21.5%) and 12 (9.2%) of patients, respectively. The overall response RR (CR+PR) to len-dex was 83.1% (13.1% CR and nCR) and 76.4% for the del13q, 78.6% for t(4;14) and 58.3% for del17p patients. In univariate analysis the time-to-progression (TTP) hazard ratio (HR) for del(13q) and for t(4;14) were 1.563 (P = .0479) and 1.680 (P = .0470) respectively. However in multivariate analysis, neither the presence of either del(13q) nor t(4;14) did adversely affect TTP. Similarly neither of these genomic aberrations did affect overall survival (OS) hazard ratio with HR= 1.472 (P= .1507) for del(13q) and HR=1.091 (P = .788) for t(4;14). TTP (HR 2.626, P = .0032) and OS (HR 3.213, P =0.0016) were significantly worse with del(17p13) in univariate and multivariate analysis. Among the other variables studied prior thalidomide exposure did result in a shorter TTP (HR= 2.330; P = .0004) but not OS (HR= 1.690; P = .0612).Conclusion: Lenalidomide plus dexamethasone can overcome the negative prognostic effect of high-risk cytogenetic abnormalities conferred by the presence of del(13q) and t(4;14), and represents a good treatment option for relapsed or refractory MM patients with these adverse cytogenetic profiles. (Clinicaltrials.gov number, NCT00179647.)

Lenalidomide Overcomes Poor Prognosis Conferred by del13q and t(4;14) but Not del17p13 in Multiple Myeloma: Results of the Canadian MM016 Trial.

The outcome of conventional therapy in MM is highly heterogeneous and appears to be largely dictated by the presence of recurrent genomic aberrations. Among these t(4;14), deletion 17p13 (TP53 locus), maf gene translocations and to a lesser extent del13q define a subgroup of patients with high risk disease. We here report on the efficacy (RR, PFS and OS) of lenalidomide and dexamethasone (len-dex) in relapsed MM patients according to their del13q, t(4;14) and del17p13 status. The MM016 is a multicenter single arm open label expanded access program for len in relapsed and refractory MM. Pts received dex orally (40mg, days 1–4; 9–12 and 17–20 for 4 cycles, then days 1–4 beginning with cycle 5) and len 25mg orally on days 1–21 of a 28 days cycle. FISH studies with commercially available probes detected the presence or absence of del13q, t(4;14)(p16;q32) and del17p13 on the interphase bone marrow aspirates. Blade criteria were used to define RR. PFS and OS were defined according to the international uniform response criteria. 159 patients with FISH results available for a least one of the genomic aberrations were included in this analysis: median age was 61 yrs (32–85), 50.3% had ISS stage II or III, median beta2-microglobulin was 3.055 mg/L (0.69–17.5), median number of prior treatments was 3 (1–6) with 50.3% previously treated with thalidomide, 43.7% with bortezomib and 73% with SCT. Del13q, t(4;14) and del17p13 were detected in 57 (37.3%), 21(19.1%) and 11 (11.6%) of patients, respectively. The overall response RR (CR+PR) to len-dex was 77.3% (14.4% CR and nCR) and 64.9% for the del13q, 76.2% for t(4;14) and 63.6% for del17p patients. The median PFS was 10.56 months (95%C.I.[6.65–14.48]). The median OS was not reached at the time of this analysis with 55.4% alive at a median follow-up of 16 months. PFS and OS were also similar when results were analyzed according to the presence or absence of del13q, t(4;14), ISS stage and prior SCT. In univariate analysis, prior thalidomide or bortezomib exposure, number of prior lines of therapy, depth of response (CR vs PR) and the presence of del17p13 by FISH did result in lower PFS and OS. However in multivariate analysis only the presence of 17p13 deletion and the depth of response correlated with PFS and OS (Table). Treatment with len-dex overcomes the poor prognosis conferred by t(4;14), high beta2-microglobulin and del13q in relapsed and refractory MM. Patients with deletion of the TP53 locus still fare very poorly despite a rapid initial response to len-dex. Confirmation of these results in patients with del17p13 with a larger prospective study is clearly warranted.VariablePFSOSHR, 95% CIp valueHR, 95% CIp valuet(4;14)0.92(0.29–2.13)0.9201.26(0.46–3.420.641Del 130.90 (0.44–1.83)0.7830.56 (0.25–1.29)0.179Del17p136.26 (2.48–15.77)0.0003.83(1.34–10.93)0.012ISS III2.03 (0.42–9.82)0.3761.72 (0.39–11.33)0.378Prior Thal1.12 (0.51–2.44)0.7681.22 (0.53–2.82)0.633Prior Bortez1.29 (0.61–2.74)0.5011.66 (0.74–3.71)0.215Response ≤ PR vs CR3.031 (2.14–4.27)0.0002.17 (1.50–3.12)0.000

Lenalidomide Overcomes Poor Prognosis Conferred by Deletion of Chromosome 13 and t(4;14) in Multiple Myeloma: MM016 Trial.

Background: Deletion of chromosome 13 (del13) and t(4;14) in multiple myeloma (MM) predicts poor response and shortened survival. Combination of Lenalidomide and Dexamethasone (Len/Dex) in two large randomized trials demonstrated superior activity and outcomes in relapsed and refractory MM patients when compared to dexamethasone monotherapy. Here we report the efficacy (response rate RR and 6 mos event free survival EFS) of Lenalidomide in MM patients, according to their del13 and t(4;14) status.Methods: The MM016 trial is a multicenter single-arm open label expanded access program for Lenalidmide in previously treated MM. Pts received Dex 40 mg orally days 1–4, 9–12, 17–20 and Len 25 mg daily orally on days 1–21 of 28Day cycle. Beginning with cycle 5, Dex was reduced to 40 mg days 1–4 only. Fluorescence in situ hybridization (FISH) detected the presence or absence of deletion 13 and t(4;14) on interphase bone marrow aspirates obtained either at the time of initial diagnosis or relapse. Commercially available FISH probes were used to detect of del13q (D13S15 and D13S319) and t(4;14)(p16;q32) (LSI FGFR3 and LSI IGH). EBMT/IBMTR criteria were used to define RR. EFS was defined as the time from initiation of treatment with Len/Dex to the first occurrence of disease relapse, progression, death from any cause as of the date of this analysis (July 4, 2006).Results: To date 36 patients were enrolled at our site: median age was 61 yrs (41–76), median time from diagnosis was 77.5 months (range: 19.5–3018) median β2 microglobulin 4.1 mg/dl (1.3–17.5), median number of prior treatments of 2 (2–4) with 11 patients (31%) previously treated with Thalidomide, 23 (64%) with Bortezomib and 44.5 % had ASCT. Del 13 and t(4;14) were detected in 16(44.5%) and 7(19.4%) patients respectively. 6/16 (37.5%) with del13 also had t(4;14) as opposed to only 1 patient (5%) in the no del13 group. The del13 vs no del13 groups were balanced with respect to major prognostic factors (age, albumin, DS stage, and lines of prior therapy); β2 microglobulin was higher in the del 13 group (median 5.2 vs 3.3). The overall response RR (CR+PR) to Len/Dex was 83%, 90% for the no del13 group and 75% in the del 13 group. At the time of this analysis 8 events (6 deaths, 2 relapses) have occurred (22%), 5 in the non del13 group. EFS estimates at 6 months were similar in the 2 groups [non del13: 73% vs 81% with del13; p=0.61]. The RR (CR+PR) for t(4;14) and non t(4;14) groups were also identical (71.5% and 86% respectively) with similar 6 mos EFS [71.4% vs. 72.4%; p=0.66]. EFS was also similar when results were analyzed according to age (< or > 65), prior transplant or prior thalidomide.Conclusion: Treatment with Lenalidomide with Dexamethasone may overcome the poor prognosis conferred by deletion 13 and/or t (4; 14) relative to event free survival and response rate. Updated results from a longer follow-up will be presented at the meeting.

603 Peginterferon α-2a (40 kDa) plus ribavirin in chronic hepatitis C patients who failed previous interferon-based therapy: Results of a multicentre open-label expanded access program in Canada

603 Peginterferon α-2a (40 kDa) plus ribavirin in chronic hepatitis C patients who failed previous interferon-based therapy: Results of a multicentre open-label expanded access program in Canada

Increased Zidovudine Prescribing Associated With Lamivudine Availability

To the Editor. —We previously described a significant decrease in zidovudine use in British Columbia following the announcement of the Concorde Trial during the first quarter of 1993. 1 We conducted the present analysis to assess recent rates of prescribing zidovudine in the province. The distribution of antiretroviral drugs in British Columbia is free of charge through the provincial Centre for Excellence in HIV/ AIDS [human immunodeficiency virus/acquired immunodeficiency syndrome] Treatment Program. 1 For physicians to prescribe zidovudine, they must complete a patient enrollment form that serves as the drug prescription. This application is accompanied by a CD4 cell count determination. Individuals infected with HIV are eligible to receive zidovudine from this program if they have at least one CD4 cell count less than 0.50×10 9 /L (500/μL). There is no other legal source of zidovudine in the province. Lamivudine (3TC, Epivir) first became available through an open-label expanded-access program