The OBR Blog

December 12, 2013 - 02:12 pm Posted in SABCS Conference Coverage comments0 Comments

Endocrine therapy is a mainstay of therapy for breast cancer patients with estrogen receptor (ER) and/or progesterone receptor (PR) positive disease, with use in the adjuvant setting for early stage disease as well as in the metastatic setting.  In the first-line metastatic setting, aromatase inhibitors (AI) can offer clinical benefit in post-menopausal ER+/PR+ patients, with progression-free survival (PFS) in clinical trials ranging from eight to 10 months.1 However, patients will eventually become resistant to endocrine therapy such as AIs, and that point, treatment often needs to shift to use of the more toxic chemotherapy options.

In recent years, as researchers have started to better understand the ER’s interaction with other cellular signaling pathways and the role that cross-talk between these pathways and the ER may play in the development of resistance to endocrine therapy, there has been increasing interest in and investigation of the ability of targeted therapies in combination with endocrine therapy to improve outcomes in ER+ patients, potentially through postponing the development of resistance or “re-sensitizing” patients with acquired resistance.

Sprycel® (dasatinib, Bristol-Myers Squibb) is a multi-targeted tyrosine kinase inhibitor that is currently approved for use in chronic myeloid leukemia (CML) and Ph+ acute lymphoblastic leukemia. Sprycel inhibits the Bcr-Abl fusion protein that is present in CML patients. However, it is also known to inhibit c-KIT, PDGFR, Ephrin, and Src kinases.  Because there is evidence that Src interacts with the ER and may potentially play a role in the development of hormonal resistance,2 Sprycel was investigated in ER+ breast cancer patients.

A Phase II trial evaluated the efficacy and safety of first-line Sprycel in combination with the AI letrozole and results were presented at the 2013 San Antonio Breast Cancer Symposium (SABCS) meeting on the morning of Thursday, December 12.3 In this trial, post-menopausal, ER+, HER2- patients with metastatic breast cancer (mBC) who were AI-naïve were randomized to receive either letrozole alone (n=63) or letrozole plus Sprycel (n=57).  Of patients who had received prior therapy in the adjuvant setting, 39% and 48% of patients in the Sprycel plus letrozole and letrozole alone arms, respectively, had received adjuvant chemotherapy; 32% and 37% of patients, respectively, had received adjuvant tamoxifen. A very small minority of patients (2% in Sprycel plus letrozole and 10% in letrozole alone arms) received an AI in the adjuvant setting, but these patients were required to have stopped adjuvant AI therapy at least a year before entry into the study.

The combination of Sprycel plus letrozole showed very promising clinical activity. The median PFS in patients who received Sprycel plus letrozole was 20.1 months, more than double the median PFS of 9.9 months seen in patients who received letrozole alone (see Table 1). This was a non-comparative trial that was not designed for a comparison between treatment arms; however, there was an exploratory PFS hazard ratio of 0.69. In contrast, the Sprycel plus letrozole combination did not appear to offer any major improvement in clinical benefit rate (CBR; objective responses plus stable disease) over letrozole alone (71% vs. 66%). There appeared to be more limited benefit in patients who had received prior letrozole, as patients who crossed over from the letrozole arm to the Sprycel plus letrozole arm upon progression had a clinical benefit rate of 23%.

As would be expected, the addition of Sprycel to letrozole treatment did add some toxicity, and 26% of patients in the Sprycel plus letrozole arm required a Sprycel dose reduction. However, Sprycel was generally well-tolerated and there were no new safety signals compared to the general safety profile that has been observed in CML patients. The most commonly observed adverse events (AEs) were fatigue, rash, nausea, edema, and neutropenia.

The strong efficacy results from this trial could support a move into Phase III development, but BMS’ development plans for Sprycel in this setting are not currently known. If Sprycel does move into Phase III development, it will enter an increasingly competitive corner of the market. Based on the results of the Phase III BOLERO-2 trial,4 the mTOR inhibitor Afinitor® (everolimus, Novartis) was approved in July 2012 in the United States and the European Union for use in post-menopausal ER+/PR+ and HER2- patients who have received prior treatment with an AI (i.e., second-line treatment or later).  The pan-PI3K inhibitor buparlisib (BKM120, Novartis) is also being investigated in two Phase III trials in the second- and third-line settings. The BELLE-2 trial is evaluating Faslodex with or without buparlisib in post-menopausal ER+/HER2- patients who have received prior treatment with an AI, and the BELLE-3 trial is evaluating Faslodex with or without buparlisib in post-menopausal ER+/HER2- patients who have received prior treatment with an AI as well as an mTOR inhibitor (most likely Afinitor).

Both Afinitor and buparlisib are currently positioned for relapsed/refractory metastatic ER+/HER2- patients, and if Sprycel were to enter Phase III development in the first-line metastatic ER+/HER2- setting, it wouldn’t be competing in the same line of therapy as these agents. However, it would be competing directly with palbociclib, the CDK 4/6 inhibitor that has received Breakthrough Therapy status from the U.S. Food and Drug Administration (FDA). Palbociclib is currently being evaluated in combination with letrozole in a Phase III trial in first-line ER+/HER2- metastatic patients.

How does the efficacy data for Sprycel stack up against that for palbociclib? As would be expected considering its Breakthrough Therapy designation, the Phase II data for palbociclib set an extremely high bar for efficacy in this setting, and the initial Phase II results for palbociclib was one of the most-discussed presentation of the 2012 SABCS annual meeting. In this Phase II trial, the addition of palbociclib to letrozole as first-line therapy for post-menopausal ER+/HER2- metastatic patients significantly improved PFS from 7.5 months to 26.1 months, with an impressive hazard ratio of 0.37 (p<0.001).5 In addition, the clinical benefit rate was increased from 44% in the letrozole alone arm to 70% in the palbociclib plus letrozole arm. While the Phase II data presented for Sprycel plus letrozole do not match this high benchmark, the median PFS of 20.1 comes quite close to the remarkable 26.1 month median PFS for palbociclib. While Sprycel would not be likely to outcompete palbociclib on efficacy based on these results alone, it is always possible that the situation could change with results from a Phase III trial, and the promising PFS result for Sprycel certainly provides hope that this strategy for combining hormone therapy with targeted therapies will prove to have a major impact on outcomes for ER+/HER2- patients with metastatic disease.

As hormone therapy generally has a relatively benign safety profile, safety will also be another major factor when physicians are considering whether to add a targeted therapy to hormone therapy in metastatic ER+/HER2- patients.  While Sprycel is clearly well-tolerated enough to be administered to CML patients for relatively long durations, palbociclib was also generally well-tolerated. However, in the Phase II trial, the addition of palbociclib did markedly increase the incidence of Grade 3/4 neutropenia compared to letrozole alone (51% vs. 1%). Therefore, Sprycel could potentially end up with a slight advantage over palbociclib in terms of safety. In this patient population, where physicians attempt to prolong the time on hormone therapy in order to avoid the poor safety profiles of the more toxic chemotherapy regimens, safety will likely play a major role in physicians’ decisions among available agents.

Although the landscape for the treatment of post-menopausal, metastatic ER+/HER2- breast cancer patients is clearly on track to become a crowded market in the future, the increasing number of agents in development offer the hope of significant advances in outcomes for these patients in upcoming years.

By: Stephanie Hawthorne, PhD, Director, Clinical and Scientific Assessment, Kantar Health and Cory Blaiss, PhD, Analyst, Clinical and Scientific Assessment, Kantar Health


  1. Bonneterre, JCO, 2001; Nabholtz, JCO, 2003; Mouridsen, JCO, 2003
  2. Vallabhaneni et al., Breast Cancer Res, 2011; Renoir et al., Biochem Pharmacol, 2013
  3. Paul et al., SABCS 2013, Abstract S3-07
  4. Baselga et al., NEJM, 2012
  5. Finn et al., SABCS 2012, Abstract S1-06

December 10, 2013 - 10:12 am Posted in ASH Conference Coverage comments0 Comments

Today, on the final day of the annual meeting of the American Society of Hematology (ASH), Richard Furman presented exciting results from a planned interim analysis of a Phase III, randomized double-blind, placebo-controlled study evaluating efficacy and safety of idelalisib (GS-1101, Gilead Sciences) and Rituxan® (rituximab, Genentech/Roche) for previously-treated patients with chronic lymphocytic leukemia (CLL)1. Patients who have relapsed following prior treatment of their CLL frequently have few therapeutic options, may have co-morbidities or poor renal/bone marrow function that preclude administration of highly toxic chemotherapies, and relapsed CLL is often associated with adverse cytogenetics that renders the disease unresponsive to available therapies. Thus, there remains a great need for novel therapies for relapsed CLL patients who are unable to tolerate chemotherapy. Phase III trials in CLL are ongoing or recently completed for Arzerra® (ofatumumab, GlaxoSmithKline), ibrutinib (BTK inhibitor, Pharmacyclics/Johnson & Johnson), and Gazyva® (obinutuzumab, Genentech/Roche), and several other new agents may be entering Phase III development soon based on encouraging early-stage data reported at ASH 2013. We previously reported on the very promising results of Gazyva and Arzerra in their pivotal trials that were presented at ASH 2013, and the idelalisib results further add to the CLL excitement that permeated the conference this year.

Idelalisib is a first-in-class, oral small molecule that is a highly selective inhibitor of the delta isoform of phosphatidalyinositol-3-kinase (PI3K-δ). Idelalisib inhibits homing and retention of CLL cells in lymphoid tissues, restrains proliferation and induces apoptosis in CLL cells. In the Phase III Study 116 trial, patients with relapsed CLL deemed “unfit” for further chemotherapy, who progressed less than 24 months since their last therapy, and who had received one or more anti-CD20 antibody-containing therapies or two or more cytotoxic therapies were eligible for this trial. Patients were randomized to receive six months of therapy with idelalisib plus Rituxan (n=110) or with Rituxan plus placebo (n=110). Median PFS was not reached for the idelalisib arm and was 5.5 months for the Rituxan/placebo arm; however, PFS at 24 weeks was 93% versus 46% (HR 0.15; p<0001), respectively. Idelalisib also significantly improved overall response rate (81% for the idelalisib arm versus 13% for the placebo arm; p<0.0001), and overall survival (HR=0.28; p=0.018). The combination of idelalisib plus Rituxan had an acceptable adverse event (AE) profile, with Grade ≥3 AEs reported in 56% of patients compared to 48% in the Rituxan/placebo arm. The most common AEs included transaminitis, pyrexia, fatigue, nausea, chills, diarrhea and infusion-related reaction. Based upon a review of interim efficacy and safety data, the data monitoring committee recommended stopping this study early.

These are the first randomized data for idelalisib and follow on the heels of pivotal Phase II data for the drug in of indolent non-Hodgkin’s lymphoma (iNHL), and also supported FDA Breakthrough Therapy Status, which was granted in Q4 2013. Gilead Sciences has already filed for regulatory approval in relapsed/refractory iNHL with the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA). Based on the results of Study 116, Gilead has also filed for approved in relapsed/refractory CLL with the EMA, and is in discussions for filing with the FDA.

CLL is poised for major changes in the coming years with the advent of novel targeted therapies. With multiple novel agents rapidly advancing toward approval for treatment of CLL, the stage is set for an epic battle. Perhaps the fiercest advisories in the CLL market will be idelalisib versus the Bruton’s tyrosine kinase inhibitor (BTKi) Imbruvica® (ibrutinib, Pharmacyclics/Janssen). The companies developing these agents have different goals for each of these agents. Janssen hopes that the promising efficacy data with Imbruvica will be repeated in Phase III trials and helps Imbruvica become the natural standard to replace Arzerra in the relapsed setting or to become the key combination partner with chemoimmunotherapy. Gilead instead has chosen to pursue the development of idelalisib as an ideal combination partner with chemoimmunotherapy. Both of these targeted therapies are very well-tolerated compared to chemotherapy making them very lucrative partners or candidates for CLL. But several other challengers are also waiting in the wings, based on promising data reported during the  ASH 2013, including ABT-199 (GDC-199, Abbvie/Genentech/Roche), CTL019 (Novartis), and IPI-145 (Infinity Pharmaceuticals). IT’s certainly an exciting time for CLL development!


1. Furman et al., Abstract LBA6, ASH 2013

By: Stephanie Hawthorne, PhD, Director, Clinical and Scientific Assessment, Kantar Health and Greg Wolfe, PhD, Senior Consultant, Clinical and Scientific Assessment, Kantar Health

December 10, 2013 - 10:12 am Posted in ASH Conference Coverage comments0 Comments

The 2013 American Society for Hematology (ASH) meeting is ripe with new data in the treatment of chronic lymphocytic leukemia (CLL), with particular focus on high unmet need populations, such as relapsed/refractory disease and patients “unfit” for intensive chemoimmunotherapy. Impressive results from the Phase III CLL11 trial of Gazyva® (obinutuzumab, Genentech/Roche) were presented in during the plenary session on December 8.1 On December 9, two back-to-back oral sessions highlighted several other advances in the treatment of CLL, including results from the Phase III COMPLEMENT-1 trial of Arzerra.2

The Phase III COMPLEMENT-1 trial (NCT00748189) was a randomized study of Arzerra plus chlorambucil versus chlorambucil monotherapy in 447 previously untreated chemo-ineligible CLL patients. Progression-free survival (PFS; the primary endpoint) was significantly improved, with a 71% reduction in risk of progression or death and a 22.4-month median PFS (versus 13.1 months in the control arm; HR 0.57, p=0.001). The overall response rate (ORR), complete response rate (CR), and high rate of minimal residual disease (MRD) negativity also all favored the Arzerra arm. While the overall survival does numerically favor Arzerra, the data is immature and no conclusions can be drawn at this time. A slightly higher incidence of Grade 3/4 adverse events (AEs) was reported in the Arzerra arm (50% of patients) versus the chlorambucil arm (43%). Infusion-related reactions (10% versus n/a, respectively), neutropenia (26% versus 14%) and thrombocytopenia (5% versus 10%) represented the major differences in Grade 3/4 AEs.

The COMPLEMENT-1 trial was clearly positive, adding to the growing data supporting the use of new combination regimens in patients considered “unfit” for intensive chemoinnumotherapy. These data supported U.S. Food and Drug Administration (FDA) and European Medicine Agency (EMA) regulatory applications in October 2013 for approval of Arzerra plus chlorambucil in first-line fludarabine-ineligible CLL, and successful approval is highly likely. In addition, this data supported the FDA granting Arzerra Breakthrough Therapy Status in September 2013, a coveted designation that is also held by several other agents in development in CLL: Gazyva, idelalisib (Gilead), and Imbruvica® (ibrutinib, Pharmacyclics/Johnson & Johnson). However, approval does not guarantee adoption. As the third anti-CD20 mAb to arrive on the CLL scene, can Arzerra distinguish itself in this rapidly crowding indication?

Results presented at the 2013 American Society of Clinical Oncology (ASCO) annual meeting this year3 served as the basis for an early (November 1, 2013) approval of Gazyva in combination with chlorambucil in newly diagnosed CLL patients with comorbidities that make them unfit for standard chemotherapy. Now, with impressive updated results and a head-to-head comparison to Rituxan in hand, Genentech/Roche is well positioned for the eventual displacement of Rituxan as a standard of care in B-cell malignancies (conveniently coinciding with rituximab patent expiration). The Phase III CLL11 trial (NCT01010061) was a three-arm study that randomized patients 1:2:2 to treatment with chlorambucil alone, chlorambucil plus Gazyva, or chlorambucil plus Rituxan. Unlike the CLL11 study, the COMPLEMENT-1 trial design lacks a comparison to Rituxan, which is a more stringent comparator than chlorambucil alone – a step that was questioned by the audience members and may cost GlaxoSmithKline market share in the future.

While it is tempting to do a cross trial comparison (see Table 1), each trial enrolled different patients and used different dosing of chlorambucil. The CLL11 study used once every two weeks dosing of 0.5mg/kg, whereas the COMPLEMENT-1 trial used a dose of 10 mg/m2 on days 1-7. This increased chlorambucil exposure in the Arzerra trial might explain why the control arm in COMPLEMENT-1 performed better than in CLL11. The level of benefit in COMPLEMENT-1 was impressive, although it may have been overshadowed by the Gazyva data presented the prior day. With the caveats of cross-trial comparison mentioned above, physicians will still likely look to the raw numbers and see a difference in PFS at the median (26.7 months with Gazyva-chlorambucil and 22.4 months with Arzerra-chlormabucil) and in the overall level of PFS benefit (HR 0.18 and HR 0.57, respectively). Furthermore, there is a significant OS benefit when comparing Gazyva-chlorambucil versus chlorambucil (HR 0.41, p=0.0022), which Arzerra has not yet demonstrated due to immaturity of the data. These efficacy comparisons seem to favor Gazyva, especially in the presence of data showing significant benefit compared to Rituxan-chlormabucil as well. On the positive side, the toxicity seems to be slightly lower with Arzerra, particularly the rates of infusion reaction and thrombocytopenia ― but will this sway physicians and ultimately drive adoption?

Physicians will soon have three anti-CD20 antibodies approved in first-line CLL to choose from, in addition to a number of novel agents in development: Imbruvica, idelalisib, and ABT-199 (GDC-199, Abbvie/Genentech/Roche), all of which are presenting very promising data at ASH 2013. As these agents enter the CLL market, a natural inclination would be to combine them with an anti-CD20 antibody. Combination may offer a good opportunity for Arzerra, especially since it appears on first blush to have lower toxicity than Gazyva. Arzerra may also have a time advantage, as it is already being studied in a Phase III trial in combination with idelalisib (NCT01659021).

The COMPLEMENT-1 results aren’t the end of high profile CLL abstracts being presented at ASH this year. Tuesday is the final day of the conference and still holds one more set of data with high anticipation ― the pivotal Phase III trial of Rituxan with or without idelalisib in relapsed/refractory CLL.4 For ASH, 2013 was most certainly the Year of CLL.


1. Goede et al., Abstract 6, ASH 2013

2. Hillmen et al., Abstract 528, ASH 2013

3. Goede et al., Abstract 7004, ASCO 2013.

4. Furman, et al., Abstract LBA6, ASH 2013

By: Stephanie Hawthorne, PhD, Director, Clinical and Scientific Assessment, Kantar Health and Mara Jeffress, PhD, Associate Consultant, Clinical and Scientific Assessment, Kantar Health

December 09, 2013 - 10:12 am Posted in ASH Conference Coverage comments0 Comments

Multiple Myeloma has had significant new advances in the past year, with the U.S. Food and Drug Administration (FDA) approval of Kyprolis® (carfilzomib, Onyx/Amgen) and the U.S. and European approvals of Pomalyst® (Imnovid® in Europe, pomalidomide, Celgene), both in the relapsed/refractory setting. The relapsed/refractory setting is poised for further evolution with the recently announced success of the PANORAMA-2 Phase III trial of panobinostat (LBH589, Novartis)1 and ongoing Phase III trials with numerous other promising agents. Although these developments in the management of relapsed/refractory disease are significant, there is still a high unmet need to delay relapse among newly-diagnosed patients. In the first-line setting, several standard options exist, and choice of therapy varies by patient characteristics (most notably by their eligibility for stem cell transplantation) and by geography. In the United States, transplant eligible patients most commonly receive a triplet regimen, RVD [Revlimid® (lenalidomide, Celgene), Velcade® (bortezomib, Millennium/Janssen), dexamethasone] whereas in Europe the standard of care remains a Velcade-based doublet2. In transplant-ineligible patients, Velcade- or Revlimid-based regimens are both commonly used in the U.S., while in Europe Velcade again remains the predominant choice of therapy2. The reason for the discordance, in part lies with the data-and compendia-supported off-label use of Revlimid in newly-diagnosed patients in the U.S., while in Europe (where Velcade has a frontline label that Revlimid does not) off-label utilization is much less common.

To support regulatory approval of Revlimid for newly-diagnosed patients in both markets, Celgene and various cooperative groups have conducted multiple studies of Revlimid in newly-diagnosed patients. The MM-015 trial (NCT00405756) was reported at the American Society of Hematology (ASH) 2012 annual meeting (Abstract 944)3, and showed that a significant improvement in progression-free survival (PFS) was obtained in transplant-ineligible patients who received the MPR-R regimen (melphalan, prednisone, Revlimid induction followed by Revlimid maintenance) compared to patients who received MP alone or MPR induction only (PFS: 31 months vs. 13 months vs. 14 months; HR 0.40, p<0.001); there was, however, no improvement in overall survival at the interim analysis. A companion study, FIRST (MM-020, NCT00689936), also evaluated the efficacy of Revlimid in newly-diagnosed transplant-ineligible patients, but with a different regimen and comparator: FIRST randomized patients to continuous RevDex until progression versus RevDex for a fixed 18 cycles (72 weeks) vs. MPT (melphalan, prednisone, thalidomide) for a fixed 12 cycles (72 weeks). A first look at the FIRST data came in the plenary session on December 8 at the 2013 ASH conference4. There was a significant improvement in PFS for patients treated with continuous RevDex compared to MPT and compared to RevDex18 (see Table 1). The Kaplan-Meyer curves for all three arms overlapped for the first 18 months of treatment, after which the continuous RevDex curve quickly separated from the curves of the other two arms. Other secondary endpoints significantly favored the continuous RevDex arm as well, most importantly that of overall survival: there was a 22% reduction in the risk of death in the continuous RevDex arm compared to the MPT arm at this interim analysis (35% of ITT events).

Treatment with RevDex was associated with some increases in adverse events (higher rates of infection, deep vein thrombosis and/or pulmonary embolism, and cataracts); the RevDex arms had markedly lower rates of neutropenia and peripheral sensory neuropathy compared to MPT. Perhaps even more important was the analysis of secondary primary malignancies (SPM). At this latest follow-up, there is no significant difference in the SPM rate among the three arms; in fact, there was a slightly lower rate of hematologic SPM in the continuous RevDex arm compared with the MPT arm. The lack of increased SPM in the RevDex arms may support the hypothesis that the worrisome SPM observed in the MM-015 trial was due to the melphalan used in that regimen rather than attributable to Revlimid.

With a significant PFS and OS benefit favoring continuous RevDex along with a safety profile that may alleviate some prior concerns regarding SPM, the FIRST trial is certainly a positive study that will have significant market impact. But just what will that market impact be? This study establishes RevDex as superior to MPT in newly-diagnosed transplant-ineligible patients. The most significant impact will be that the results are likely to support regulatory approval of Revlimid in the first-line setting in both the U.S. and Europe. As noted earlier, the lack of European approval in first-line has limited Revlimid’s utilization in this setting in Europe, so gaining this label expansion will be critical for its further success. But how will treatment patterns change? Although MP-based regimens have long been considered the standard of care for transplant-ineligible patients, in reality they have very little use in the modern day: in 14% of U.S. patients and 21% of Western Europe patients2; dexamethasone-based doublets or triplets have evolved to become the preferred regimen in both transplant-eligible and -ineligible patients in recent years. So while a change in practice from MPT to RevDex is unlikely to emerge from this study and its approval, a more likely outcome is a shift in the balance between use of Velcade-based regimens and Revlimid-based regimens in newly-diagnosed patients. As mentioned above, Velcade-based regimens are heavily utilized in Europe, due to the OS benefit as demonstrated in multiple Phase III trials5,6. With Revlimid now able to claim an OS benefit in frontline, a shift in treatment patterns may emerge, with RevDex posing a new competitive threat to VelDex in Europe and posing a renewed competitive threat to VelDex in the U.S. How do the two regimens compare? VelDex has not been extensively studied in transplant-ineligible patients, so a comparison of efficacy and safety outcomes between these two regimens is not possible. In the Phase III VISTA trial in newly-diagnosed transplant- ineligible patients, Velcade + MP (VMP) resulted in a 24 month median time to progression (TTP) and 69% 3-year OS5. The 32.5 month median TTP of RevDex in the FIRST trial4 and the 31 month PFS of MPR-R in the MM-015 trial3 (TTP was not reported) compare favorably with the 24 months reported for VMP; OS may be comparable or slightly favoring RevDex (~75% if we extrapolate 3-year OS from the Kaplan-Meyer curve presented by Dr. Facon4) and is comparable for MPR-R (70%)3. Acknowledging the weaknesses in these cross-trial comparisons, they do at least suggest the possibility for RevDex to become adopted as a new standard of care in newly-diagnosed transplant-ineligible myeloma, and most certainly will support regulatory approval by the European Medicines Agency and the FDA. Regulatory approval for Revlimid in the first-line setting will not only impact its utilization, but also that of several agents and new regimens in development that build off of a Revlimid-based backbone in first-line. Advancements may be making greater leaps and bounds in the relapsed/refractory setting, but first-line treatments continue to progress at a slow and steady pace, and in the end, it’s the patients who reap the rewards.


  1. Novartis press release, December 6, 2013
  2. Kantar Health, CancerMPact® Treatment Architecture U.S. and Western Europe, accessed December 8, 2013
  3. Dimopoulos et al., Abstract 944, ASH 2012; Palumbo, et al., N Engl J Med; 366:1759-1769, 2012
  4. Facon et al., Abstract 2, ASH 2013
  5. San Miguel et al., N Engl J Med; 359:906-91, 2008
  6. Harousseau et al., J Clin Oncol, 28: 4621-4629, 2010

By: Stephanie Hawthorne, PhD, Director, Clinical and Scientific Assessment, Kantar Health

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