Agent Induction Therapy Research Articles

Tandem Autologous Stem Cell Transplantation Does Not Benefit High-Risk Myeloma Patients in the Maintenance Era: Real-World Results from The Canadian Myeloma Research Group Database

In patients with multiple myeloma (MM), the presence of high-risk cytogenetic abnormalities is associated with worse disease control and survival. Autologous stem cell transplant (ASCT) does benefit these patients. Tandem transplantation has been explored as a means to deepen responses and further improve survival however, its role remains controversial. This is particularly true in the era of novel agent induction and post-transplant maintenance therapy. The aim of this study was to use the Canadian Myeloma Research Group database and examine a large cohort of real-world patients comparing the outcomes of tandem versus single ASCT specifically in high-risk patients receiving novel agent-based induction and post-transplant maintenance. The data for this study was derived retrospectively from a comprehensive national-level database of Canadian patients with MM. High-risk cytogenetics was defined as presence of del17p, t(4;14), or t(14;16). Those receiving allogeneic transplant were excluded. Tandem transplantation was defined as a second ASCT performed consecutively without interim relapse or progression after first ASCT. Those with relapse or progressive disease within 3 months of completing a first transplant were excluded. We compared response depth, progression-free, and overall survival (OS) based on single or tandem transplantation procedures. The impact of covariates of interest was also assessed. A total of 381 patients with high-risk cytogenetics were identified. A total of 242 received single and 139 patients received tandem transplants. All received post-transplant maintenance. The most common induction regimen for these patients was cyclophosphamide, bortezomib, and steroids (CyBorD, 87%). Forty-one patients (10.8%) required reinduction prior to first ASCT. The best overall responses at any time were 98.3% (90.5% ≥ very good partial response [VGPR]) and 98.6% (89.9% ≥ VGPR) in the single and tandem ASCT groups, respectively. Survival outcomes were similar with the median progression-free survival for single or tandem ASCT of 35.2 and 35.3 months (P = .88) and the median OS were 92.6 and 88.9 months, respectively (P = .72). No statistically significant differences were seen based on type of cytogenetic abnormality or type of maintenance. This was confirmed on multivariate analysis. In the real-world setting, tandem ASCT does not improve outcomes for MM patients with high-risk cytogenetics. This may be driven by the use of effective pre- and post-ASCT therapies. The development of more potent induction and consolidation along with current nearly ubiquitous continuous maintenance therapies until disease progression does not support the use of a second high-dose procedure.

Investigation of the immune profile of multiple myeloma patients achieving long-term survival after autologous stem cell transplantation

Objective: To identify the characteristics of the bone marrow immune microenvironment associated with long-term survival in multiple myeloma (MM) patients. Methods: In the follow-up cohort of patients with newly diagnosed MM and who received "novel agent induction therapy and subsequent autologous stem cell transplantation and immunomodulator maintenance therapy" in the First Affiliated Hospital of Sun Yat-sen University, a cross-sectional study was carried out between August 2019 and May 2020. Using NanoString technology, the RNA expression of 770 bone marrow immune-related markers was compared between 16 patients who had progression-free survival ≥5 years and 5 patients with progressive disease. Among the 16 patients who achieved long-term survival, 9 achieved persistent minimal residual disease (MRD) negative while the other 7 had persistent positive MRD. The functional scores of each kind of immune cells were calculated based on the expression level of characteristic genes, so as to indirectly obtained the proportion of each immune cell subset. The Mann-Whitney U test and the Kruskal Wallis test were used for statistical analysis. Results: The proportion of neutrophils was significantly higher in long-surviving MM patients than in patients with progressive disease [functional scores, 13.61 (13.33, 14.25) vs. 12.93 (12.58, 13.38); Z=2.31, P=0.021]. Among long-surviving patients, those who were MRD-positive had a significantly greater number of mast cells compared with those who were MRD-negative [functional scores, 7.09 (6.49, 8.57) vs. 6.03 (5.18, 6.69); H=2.18, P=0.029]. Compared with patients with progressive disease, four genes (CTSG, IFIT2, S100B, and CHIT1) were significantly downregulated and six (C4B, TNFRSF17, CD70, IRF4, C2, and GAGE1) were upregulated in long-surviving patients. Among long-surviving patients, only gene CMA1 was significantly upgraded, 10 genes (ISG15, OAS3, MX1, IFIT2, DDX58, SIGLEC1, CXCL10, IL1RN, SERPING and TNFSF10) were significantly downregulated in the MRD-positive group compared with that in the MRD-negative group, the first 5 of which are related to the interferon response pathway. Conclusions: The increased neutrophil and mast cell numbers may be related to long-term survival in MM. Interferon signaling activation may be a key bone marrow immune profiling feature for MRD-negative, long-surviving patients with MM.

Prognostic nomogram for multiple myeloma early relapse after autologous stem cell transplant in the novel agent era.

The present study intended to establish a predictive nomogram for early relapse (ER) (<12 months) after autologous stem cell transplantation (ASCT) in the novel drug era for multiple myeloma (MM). The nomogram was designed and constructed to a retrospective clinical data of newly diagnosed MM patients received novel agent induction therapy and subsequent ASCT at three centers in China from July 2007 to December 2018. The retrospective study was conducted among 294 patients in the training cohort and 126 in the validation cohort. The nomogram's predictive accuracy was evaluated by the concordance index, calibration curve and decision clinical curve. The study cohort included 420 newly diagnosed MM patients, and 100 (23.8%) were identified as having ER, including 74 in the training cohort and 26 in the validation cohort. According to the result of multivariate regression in the training cohort, the prognostic variables included in the nomogram were high-risk cytogenetics, LDH > UNL, and response less than very good partial response (VGPR) after ASCT. The calibration curve showed good fitness between the nomogram predictions and the actual observations and the nomogram was further validated by a clinical decision curve. The nomogram's C-index achieved 0.75 (95% CI, 0.70-0.80), which was higher than that of the Revised International Staging System (R-ISS) (0.62), ISS (0.59), and Durie-Salmon (DS) staging system (0.52). The discrimination ability of the nomogram in the validation cohort was superior to that of the other staging systems (C-index: 0.73 vs. R-ISS (0.54), ISS (0.55), and DS staging system (0.53)). DCA showed the prediction nomogram adds much more clinical utility. Different scores of the nomogram draw a distinction of OS. The present nomogram could serve as a feasible and accurate prediction of ER in novel drug induction transplantation-eligible MM patients, which could help modify the post-ASCT strategy for patients at high risk of ER.

Deepening Responses after Upfront Autologous Stem Cell Transplantation in Patients with Newly Diagnosed Multiple Myeloma in the Era of Novel Agent Induction Therapy

High-dose melphalan followed by autologous stem cell transplantation (ASCT) remains the standard of care for transplant-eligible patients with newly diagnosed multiple myeloma (NDMM). Achievement of complete response (CR) and minimal residual disease (MRD) negativity are associated with improved progression-free survival (PFS) and overall survival (OS). With superior triplet- and quadruplet-based induction regimens, a higher proportion of patients are achieving deep responses of at least a very good partial response (VGPR) or better. The probability of achieving different levels of deeper hematologic responses post-ASCT based on the pre-ASCT depth of response is less clear in the existing literature but would be of value to patients and providers in discussing the added benefit of ASCT. We assessed the rate of deepening the hematologic response with upfront ASCT in patients with NDMM, mainly to MRD-negative CR, based on the response achieved after induction therapy. We retrospectively reviewed 210 patients with NDMM who underwent upfront ASCT at Mayo Clinic Rochester between May 1, 2018, and July 31, 2019. In addition to the availability of next-generation flow cytometry (NGF) testing for MRD status, which yielded a sensitivity of 10-5, the more sensitive mass spectrometry-based assessment of peripheral blood (ie, MASS-FIX) for monoclonal proteins was used rather than conventional immunofixation. Pre-ASCT, 23 patients (11%) achieved MRD-negative CR, which increased to 66 patients (31%) post-ASCT. Of 187 patients not in MRD-negative CR pre-ASCT, 45 (24%) converted to MRD-negative CR. Patients with MRD-positive CR before ASCT had the highest rates of conversion to MRD-negative CR. HR cytogenetics did not impact rates of MRD-negative CR achievement post-ASCT irrespective of pre-ASCT IMWG response (P=1.0). Overall, irrespective of IMWG response, 43 patients (20%) were MRD-negative pre-ASCT (19 in VGPR, 24 in CR or sCR), and 102 patients (49%) were MRD-negative post-ASCT (36 in VGPR, 66 in CR or sCR). Among 85 patients with VGPR post-ASCT, 36 achieved MRD negativity, of whom 8 (22%) progressed, whereas 49 had MRD-positive disease, of whom 24 (49%) progressed (P=.014). Upfront ASCT in patients with NDMM led to deeper responses, with 24% converting to MRD negative CR and more than doubling of the total rate of MRD negativity irrespective of IMWG response depth.

P-209: Deepening responses post upfront ASCT in newly diagnosed multiple myeloma in the era of novel agent induction therapy

P-209: Deepening responses post upfront ASCT in newly diagnosed multiple myeloma in the era of novel agent induction therapy

Body mass index and venetoclax-hypomethylating agent induction therapy for acute myeloid leukemia.

e19038 Background: Frontline Ven-HMA dosing is imperfectly estimated with HMA using body surface area (BSA) and Ven not BSA/weight-based. Not much is known if elevated body-mass-index (BMI) reduces drug exposure and impacts clinical outcomes with Ven-HMA. We sought to investigate the effectiveness of Ven-HMA in pts with elevated BMI and hypothesized no negative impact on outcomes. Methods: We retrospectively reviewed the records of pts with AML treated with frontline Ven-HMA from 12/2018-11/2021. The primary outcome was composite response rate (CR/CRi) as defined by 2017 ELN criteria. Pearson’s χ2 tests and Wilcoxon rank tests were used for bivariate analyses. Kaplan-Meier methods were used to calculate OS. Results: We identified 63 pts treated with frontline Ven-HMA, among whom 20 had a normal BMI (&lt;25 kg/m2), 27 were overweight (BMI 25-29 kg/m2), and 16 were obese (BMI&gt;30 kg/m2). Median age was 73 (range 37-89) and there were no differences in baseline patient- and disease-specific factors. The cohort overall was enriched for complex karyotype and TP53-mutated disease (46% and 33%, respectively), but without intergroup differences. Increasing BMI was associated with more HMA naivety and appeared to be associated with more antifungal use during induction (BMI &lt;25: 60%, BMI &gt;30: 88%; p=0.07) with similar rates of moderate/strong CYP3A4 inhibition. Early mortality (within 8-weeks of Ven-HMA), was greater in obese pts, but not significantly so (BMI&lt;25: 20%; BMI&gt;30: 31.3%; p=0.45). CR/CRi rate was similar among groups (BMI&lt;25: 40%; BMI 25-29: 52%; BMI&gt;30: 44%; p=0.71), as was ORR ( p=0.14). A sub-analysis excluding pts with prior HMA did not affect the parity in rate of CR/CRi in normal weight or obese pts (40% vs 44%, p=0.83) (Table). Conclusions: Our study showed that increasing BMI appears to have no negative influence on response to frontline Ven-HMA. However, it remains unclear whether increased BMI affects drug exposure, so dedicated studies are needed.[Table: see text]

NOTHING TO HIDE UP YOUR SLEEVE: A RARE PRESENTATION OF DISSEMINATED NOCARDIOSIS

TOPIC: Chest Infections TYPE: Medical Student/Resident Case Reports INTRODUCTION: Nocardia is a unique member of the order, Actinomycetales. It is a gram-positive, aerobic bacteria that is characterized by its filamentous branching that stains acid-fast. It can be found in soil and decaying vegetation, with inhalation of airborne particles being the most common mode of inoculation. Considered to be a rare, opportunistic infection, the incidence rate is approximately 500-1000 cases in the US per year (1). Although it typically leads to cutaneous disease, Nocardia has the ability to disseminate as widespread disease leading to pulmonary and CNS involvement. CASE PRESENTATION: An 81 year old African-American female with a past medical history of non-Hodgkin Lymphoma treated with radiation in 1999, hypertension, diabetes, hypothyroidism, chronic kidney disease, and heart failure with preserved ejection fraction. She presented with worsening dyspnea, orthopnea, and lower extremity swelling and was admitted for heart failure exacerbation. She was found to have multiple, painful skin abscesses. On presentation, she was septic: febrile and tachycardic with profound leukocytosis. Radiographic imaging revealed multiple, large, cystic fluid collections in the neck, bilateral arms, and left leg along with right, hilar lymphadenopathy and apical cavitary lesion in the right lung. There was a large, anterior chest wall mass communicating with the left arm lesion. IR guided biopsy ruled-out malignancy. General surgery performed I&D's of the peripheral lesions whereas Cardiothoracic Surgery performed I&D of the chest wall mass. Aerobic cultures grew gram-positive, branching bacilli that later speciated to Nocardia pneumoniae. DISCUSSION: The patient was diagnosed with Disseminated Nocardiosis with lymphocutaneous and pulmonary involvement. Our work-up was negative for CNS or bone disease. The exact etiology was unclear. She did not endorse direct trauma/inoculation at lesion sites and denied any unusual exposure to soil, decaying vegetation, or aquatic environments. Despite Nocardia's prevalence in immunocompromised hosts, our patient was determined to be immunocompetent. Fortunately, there was no evidence of recurrence of malignancy and she was HIV negative. Her treatment regimen consisted of a dual agent induction therapy for 6 weeks that was followed by a 6 month maintenance period with a single agent. However, Nocardia has a propensity to recur or progress despite appropriate antibiotic therapy and source control. CONCLUSIONS: Nocardiosis has been described as an emerging infectious disease given the higher number of HIV and transplant patients. Notably, Nocardia pneumoniae is not accounted for in 82 percent of US strains isolated between 1995 and 2004 (2). This species was first described in 2004 with either "undetermined clinical significance" versus "pulmonary disease" (3). This would be a novel presentation of disseminated Nocardia pneumoniae in an immunocompetent host. REFERENCE #1: Rawat D, Rajasurya V, Chakraborty RK, et al. Nocardiosis. [Updated 2020 Aug 10]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2021 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK526075/ REFERENCE #2: Uhde KB, Pathak S, McCullum I Jr, et al. Antimicrobial-resistant nocardia isolates, United States, 1995-2004. Clin Infect Dis 2010; 51:1445. REFERENCE #3: The Complexities of Nocardia Taxonomy and IdentificationPatricia S. Conville, Barbara A. Brown-Elliott, Terry Smith, Adrian M. ZelaznyJournal of Clinical Microbiology Dec 2017, 56 (1) e01419-17; DOI: 10.1128/JCM.01419-17 DISCLOSURES: No relevant relationships by HUY NONG, source=Web Response No relevant relationships by Michael Vu, source=Web Response

MM-315: Impact of Stratification of Levels of Serum Lactate Dehydrogenase (LDH) at Diagnosis on Overall Survival (OS) in Newly Diagnosed Multiple Myeloma (NDMM)

Context Elevated serum LDH level is an adverse prognostic factor in NDMM. Quantitative serum LDH levels range from over the upper limit of normal (ULN) to levels 2- or more-fold higher than ULN. Objective The “normal versus elevated” classification of serum LDH level can fail to discriminate between different NDMM disease biology. Thus, we attempted to further stratify NDMM patients by their serum LDH level and determine the impact on OS outcomes. Design and Setting The cohort included patients diagnosed with NDMM from the Mayo Clinic, Rochester, from 2003 to 2017, treated with novel agent induction therapy with measured serum LDH levels at the time of diagnosis. Patients The cohort consists of 1,196 NDMM patients with median age of 65 (22–95) years. R-ISS classification was available for 968 patients and is distributed as follows: 210 (22%) stage 1, 639 (66%) stage 2, and 119 (12%) stage 3. Cytogenetic risk data was available for 970 patients: 215 (22%) high-risk and 755 (78%) standard-risk. Main Outcome Measures The serum LDH levels were stratified into three levels: normal (LDH < 222 U/L), elevated (LDH 223–444 U/L), and very elevated (LDH >444 U/L). Survival analysis was performed using the Kaplan–Meier method and compared via Wilcoxon method. Results Median serum LDH level was 162 U/L (3–1260), and an elevated LDH was present in 199 patients (17%). Median OS for patients with normal (N = 997; 83%), elevated (N = 170; 13%), and very elevated (N = 29; 3%) LDH levels were 76 months, 57 months, and 23 months respectively (P < 0.001). Impact of LDH levels on OS by R-ISS stage and cytogenetic risk was analyzed, and regardless of R-ISS stage/cytogenetic risk, very elevated patients had significantly smaller median OS (discrepancy ranging from 19 months [R-ISS stage 3] to 36 months [R-ISS stage 2] than elevated patients (P ≤ 0.0022 for all classifications). Conclusion A small subset (3%) of NDMM have very elevated LDH levels that confer exceptionally poor OS, irrespective of R-ISS stage and cytogenetic risk. Future studies determining disease biology responsible for such poor OS outcomes are warranted. Acknowledgments Research was supported by the National Cancer Institute [Grant Number CA254961], the Helen Diller Family Foundation, and the Marion Schwartz Foundation for Multiple Myeloma. Elevated serum LDH level is an adverse prognostic factor in NDMM. Quantitative serum LDH levels range from over the upper limit of normal (ULN) to levels 2- or more-fold higher than ULN. The “normal versus elevated” classification of serum LDH level can fail to discriminate between different NDMM disease biology. Thus, we attempted to further stratify NDMM patients by their serum LDH level and determine the impact on OS outcomes. The cohort included patients diagnosed with NDMM from the Mayo Clinic, Rochester, from 2003 to 2017, treated with novel agent induction therapy with measured serum LDH levels at the time of diagnosis. The cohort consists of 1,196 NDMM patients with median age of 65 (22–95) years. R-ISS classification was available for 968 patients and is distributed as follows: 210 (22%) stage 1, 639 (66%) stage 2, and 119 (12%) stage 3. Cytogenetic risk data was available for 970 patients: 215 (22%) high-risk and 755 (78%) standard-risk. The serum LDH levels were stratified into three levels: normal (LDH < 222 U/L), elevated (LDH 223–444 U/L), and very elevated (LDH >444 U/L). Survival analysis was performed using the Kaplan–Meier method and compared via Wilcoxon method. Median serum LDH level was 162 U/L (3–1260), and an elevated LDH was present in 199 patients (17%). Median OS for patients with normal (N = 997; 83%), elevated (N = 170; 13%), and very elevated (N = 29; 3%) LDH levels were 76 months, 57 months, and 23 months respectively (P < 0.001). Impact of LDH levels on OS by R-ISS stage and cytogenetic risk was analyzed, and regardless of R-ISS stage/cytogenetic risk, very elevated patients had significantly smaller median OS (discrepancy ranging from 19 months [R-ISS stage 3] to 36 months [R-ISS stage 2] than elevated patients (P ≤ 0.0022 for all classifications). A small subset (3%) of NDMM have very elevated LDH levels that confer exceptionally poor OS, irrespective of R-ISS stage and cytogenetic risk. Future studies determining disease biology responsible for such poor OS outcomes are warranted.

A High- Risk Genetic Signature Is Predictive For Poor Outcome In Auto-Transplant Eigible Multiple Myeloma Patients Even With Use Of Novel Agents. A Single Institution Study

IntroductionMulti agent induction therapy followed by an auto transplant is currently the standard of care in fit patients up to the age of 70 in most haematology units. There is little data available on the actual real world uptake of this “standard of care” as many series have a significant selection bias. We were able to ascertain the true uptake of an auto transplant in a large, continuous series of all the patients referred to a single unit. AimThis study analysed the outcomes of a cohort of auto transplant eligible patients (defined as up to age 68) over a decade of treatment at one institution. Genetic analysis by karyotype (G – banding) and FISH was performed in all patients and high risk abnormalities identified. We then compared survival in the transplant and non transplant groups and performed a subset analysis according to possession of a high risk genetic signature. MethodsThe multiple myeloma database at Wellington Hospital was interrogated during the period 2002 to 2012. One hundred and forty patients were identified with an age range from 32 to 68 years. There was a male preponderance of 89 and 51 females. Conventional chromosome karyotype was done and 13q deletions were detected by this method and considered high risk. The FISH panel was comprehensive and included 13q del., t(4:14), t(14:16), p53 deletion. In the last five years 1Q gains, MYC and a hyper-diploid clone were also routine. ResultsThe 140 patients were divided into 80 receiving an auto graft and 68 did not for various reasons. The reasons included refusal, co-morbid conditions such as cardiac, respiratory and significant renal impairment. Two patients who were on dialysis were auto grafted however and not excluded.Induction treatment over the decade included VAD initially, then cyclophosphamide/ dexamethasone and then from 2008, a bortezomib based regime of Cy/Bor/D was employed. Cy/Bor/D induced patients numbered 40 or 50% of the total auto graft cohort.There were 25% high risk abnormalities detected in the auto graft group and t(4:14) was detected in 8% and p53 del. totalled 6% (6 of 80). The transplant related mortality in this group was 0% (no deaths within 100 days). The overall survival (OS) at three years was 62% and this compared with an OS of 30% in the non transplant group (P = 0.001). The non auto graft group also had a 25% (15 out of 60 ) bad risk signature rate which included three patients with t(4:14), six p53 del. (12%), one t(4:14) case and complex karyotypes in five. One patient had a t(4:14), a p53 deletion and a 1Q gain (triple hit). This patient subgroup had no survivors at the three year mark. The median OS of the non auto graft group was 16 months and has not been reached in the transplant group. ConclusionThis group of auto grafted myeloma patients has a TMR of zero which represents some of the best results reported. They had an excellent three year OS of 62% which is projected to be eventually greater than 75% when the more recently treated patients cross the three year mark.The use of bortezomib in the latest auto grafted cohort currently includes only two deaths, so this drug has resulted in CR rates approaching 40% when assessed by day 100 marrows. This study illustrates real world data and clearly shows that an auto transplant confers a significant survival advantage. The possession of a bad risk signature however is the most important predictor of an adverse outcome whether or not patients receive a transplant. Disclosures:No relevant conflicts of interest to declare.

Impact of stratifying levels of serum lactate dehydrogenase (LDH) at diagnosis on the overall survival (OS) in newly diagnosed multiple myeloma (NDMM).

e20016 Background: An elevated serum LDH level is an adverse prognostic factor in NDMM. However, this category includes quantitative serum LDH levels that range from just over the upper limit of normal (ULN) to levels that may be 2 or more-fold higher than the ULN. This binary classification of serum LDH level of “normal versus elevated” fails to discriminate between the different disease biology that exists among NDMM patients with elevated serum LDH levels. Thus, we attempted to further stratify NDMM patients by the level of their serum LDH and determine its impact on OS. Methods: The cohort included patients diagnosed with NDMM from the Mayo Clinic, Rochester from 2003 - 2017 who were treated with novel agent induction therapy and had serum LDH levels measured at the time of diagnosis. The serum LDH levels were stratified into three levels: Normal (LDH &lt; 222 U/L), Elevated (LDH 223-444 U/L), and Very Elevated (LDH &gt;444 U/L or &gt;2x upper limit of normal). Survival analysis was performed using the Kaplan-Meier survival analysis and compared via the log-rank method. Results: The cohort consists of 1,196 NDMM patients with a median age of 65 (22 – 95). R-ISS classification and cytogenetic risk were available for 968 and 970 patients respectively. The median serum LDH level was (162 U/L (3- 1260)) and an elevated LDH was present in 199 patients (17%). The median OS for patients with normal (N = 997; 83%), elevated (N = 170; 13%) and very elevated (N = 29; 3%) LDH levels were 76 months, 57 months and 23 months respectively (P &lt; 0.001). The impact of these different levels of LDH on OS by R-ISS stage and cytogenetic risk is shown in the Table. Conclusions: A very small subset of NDMM patients has very elevated LDH levels that confer an exceptionally poor OS irrespective of R-ISS stage and cytogenetic risk. Future studies elucidating their disease biology responsible for such poor OS outcomes are warranted.[Table: see text]

Homoeopathic Management of a Case of Severe Haemophilia Type A with Inhibitor Positive: Case Report

AbstractHaemophilia is an X-linked inherited immunogenetic bleeding disorder resulting from deficiency of clotting Factor VIII (haemophilia A) or Factor IX (haemophilia B). Haemophilia patients suffer from complication of developing autoantibodies/inhibitor against clotting factors used for the treatment; most commonly patients are treated with Factor VIII replacement therapy. In modern medicine, haemophiliacs with inhibitor positive status are treated with bypassing agents such as Factor VIII inhibitor bypassing agent and immune tolerance induction therapy (ITI) because such patients do not respond to traditional factor replacement therapy during an event of active bleeding. Treatment with ITI is very expensive and it requires medical expertise. Moreover, high cost of such treatment is one part of the problem, while its availability is another problem especially in developing countries. The inhibitor status among haemophilia patients is identified by conducting a blood test which measures the Bethesda units (BU) levels in the blood. In this case report, the homoeopathic management of a patient with haemophilia A severe type (Factor VIII &lt;1%), inhibitor positive (4 BU/mL), is presented. The patient underwent treatment for a span of 4 years. After closely assessing the patient's condition and applying the principles of homeopathy medicine selection, his frequent bleeding episodes were treated with homoeopathic medicines such as Hamamelis Virginica Q, Phosphorus, Arnica montana, Rhus toxicodendron, Calendula officinalis, and Pulsatilla nigricans. Intercurrent medicine—Tuberculinum bovinum—was given when the most indicated medicine failed to relieve the symptoms of the case and was given during non-bleeding phase. The medicines not only helped in reducing haemophilia-related bleeding episodes but also improved complaints of pain, relieved skin complaints, and showed improvement in overall psychological status of patient. It can be concluded that homeopathy medicines were able to successfully reduce the frequency of bleeding and intensity of pain in this patient. Owing to reduced bleeding, he required relatively a smaller number of factor replacement treatment compared with earlier when he was not taking homeopathy. Homoeopathy proved to be effective in managing severe haemophilia patient as a supportive therapy and was able to contribute toward reduced inhibitor levels in severe haemophilia patient.

What Multiple Myeloma With t(11;14) Should Be Classified Into in Novel Agent Era: Standard or Intermediate Risk?

ObjectiveTo investigate the prognostic value of t(11;14) for de novo multiple myeloma (MM) patients in novel agent era.MethodsA total of 455 patients with fluorescence in situ hybridization (FISH), before treatments from three hospitals in China, were included in the study. All patients received autologous stem cell transplantation (ASCT) after induction therapy as consolidation. High risk (HR) cytogenetics were defined as t(4;14), t(14;16), and/or del 17p.ResultsA total of 152 patients were in the HR group. Of patients without HR cytogenetics, 55 were in the t(11;14) group, and 248 were in the standard risk (SR) group without t(11;14). Gain in 1q21 was observed in 38.9% patients with t(11;14). There were no differences in median progression free survival (PFS) and overall survival (OS), respectively, between patients in the t(11;14) group and those in the SR group. Patients in the t(11;14) group had the longer median PFS and OS, respectively, compared with those in the HR group. Regardless of coexisting with 1q21 gain or not, patients in the t(11;14) group still had similar median PFS and OS compared to those in the SR group. Finally, multivariate analysis indicated that including 1q21 gain and bone marrow plasma cell with CD20 expression, no variables were found to predict the outcome of the t(11;14) group in our cohort.ConclusionsThese results confirm that outcomes of t(11;14) MM are similar to standard risk patients when they receive novel agent induction therapy consolidated by ASCT. Gain of 1q21 coexists with t(11;14) frequently. In addition, both bone marrow plasma cell with CD20 expression and 1q21 gain have no impact on median PFS or OS for patients with t(11;14).

Outcomes of patients with primary plasma cell leukemia (pPCL) in the era of novel agent therapy.

e20510 Background: pPCL is a rare and aggressive form of multiple myeloma (MM) with dismal survival outcomes compared to the remainder of MM patients. Several studies have validated the optimal cutoff for defining pPCL to be &gt;5% circulating plasma cells (cPCs) on a peripheral blood smear due to equally poor outcomes in this less restrictive cohort. We evaluated the clinical outcomes and cytogenetic features of patients diagnosed with pPCL at our institution that were treated with novel agent induction therapies. Methods: We evaluated patients with pPCL diagnosed between 2000 – 2018 (using the 5% cut off) at Mayo Clinic, Minnesota. Data was extracted from a prospectively maintained database and from the review of electronic medical records. Patients were categorized as having high risk (HR) cytogenetics if any of the following abnormalities were present: del 17p, t(4;14), t(14;16) or t(14;20). Chi-square tests and Fisher exact tests were used to compare differences between sub-groups. Survival analysis was performed by the Kaplan-Meier method and differences assessed using the log rank test. Results: This cohort consisted of 67 patients with pPCL with a median age of 62 years (range: 34-91) of which 33 (46%) were male. The median follow up was 46 months (95% CI: 41 – 90). The median bone marrow plasma cell involvement was 84% (Range: 10 – 100) and the median cPCs percentage on the peripheral blood was 23% (range: 5 - 93). Data on primary cytogenetic abnormalities were available in 60 (85%) patients and the distribution was as follows: t(11;14) – 27 (45%), t(4;14) – 5 (8%), t(14;16) – 8 (13%), t(14;20)- 3(5%) and del 17p- 15(25%). All patients received novel agent induction therapy with 36 (54%) having received autologous stem cell transplant and 4 undergoing an allogeneic stem cell transplant. The median time to next therapy (TTNT) and overall survival (OS) for all patients was 13 months (95% CI: 9 – 17) and 24 months (95% CI: 19 – 40) respectively; 16 months and 51 months for standard risk (SR) vs. 10 months and 19 months for HR (P = 0.005 for OS), when stratified by cytogenetic risk. There were only 17 (31%) patients who were alive for ≥48 months since diagnosis (i.e. twice the median OS of this cohort); The absence of high risk cytogenetics (P = 0.049) and non-elevated LDH level (P = 0.047) at diagnosis predicted for achieving this survival goal. Conclusions: The outcomes of patients diagnosed with pPCL remain poor despite the use of novel agent induction therapy. However, some patients appear to do better than expected and this phenomenon may be influenced by the presence of HR cytogenetics.

Clinical Outcomes and Cytogenetic Features of Primary Plasma Cell Leukemia (pPCL) in the Era of Novel Agent Induction Therapy

Clinical Outcomes and Cytogenetic Features of Primary Plasma Cell Leukemia (pPCL) in the Era of Novel Agent Induction Therapy

Prognostic Significance of Hospitalization Status at Second Cycle of Hypomethylating Agent Induction Therapy in Acute Myeloid Leukemia Patients Ineligible for Intensive Chemotherapy

Introduction: Hypomethylating agents (HMAs) are used as induction therapy for patients with acute myeloid leukemia (AML) who are ineligible for intensive chemotherapy. HMA therapy is frequently initiated in the hospital and some patients remain hospitalized through the initiation of cycle 2 (C2). Clinicians are often faced with the decision to administer C2 while the patient is still hospitalized, however, there is a paucity of prognostic information to guide treatment decisions in this common scenario. Methods: We conducted a retrospective review of patients diagnosed with treatment naïve, de novo and secondary AML who were ineligible for induction chemotherapy (at the discretion of the treating physician based on advanced age, comorbidities, or other reasons) at a single, tertiary, referral center. Patients were included if they received induction therapy with an HMA, including azacitidine and decitabine between 7/1/2008 and 7/1/2018. Exclusion criteria included receipt of intensive induction chemotherapy and inadequate electronic medical documentation. Patients were divided into four groups: patients who were discharged after completion of C1 and received C2 as an outpatient (discharged after C1), patients who received C1 and C2 during the same hospitalization (C1-C2 continuous hospitalization), those who received one total cycle (C1 only), and patients who received C1 as an outpatient (C1 outpatient). The groups were analyzed separately for the primary outcome of overall survival (OS), calculated by Kaplan Meier analysis. Results: Out of 105 patients identified who received an HMA, 100 patients were identified who met inclusion/exclusion criteria and their baseline characteristics are shown in Table 1. Most patients had de novo AML (39.0%), although 33.0% and 19.0% of patients had AML secondary to myelodysplastic syndrome (MDS) and myeloproliferative neoplasm (MPN), respectively. Additionally, 8 patients (8.0%) had therapy related AML. The majority of patients had an Eastern Cooperative Oncology Group (ECOG) performance status of 1 or 2 at induction. Patients who received C1 as an outpatient had a significantly better performance status than those who did not (p= 0.033) Decitabine was the most common HMA (57.0%) administered and was most often on 5-day schedule. Eight patients (8.0%) were continually hospitalized until C2, 5 because of active medical issues (most often fevers requiring intravenous antibiotics), 2 had physical debility precluding discharge home, and 1 was receiving intrathecal chemotherapy twice weekly for central nervous system involvement of AML. The median OS was 15.6 months (95% CI 2.66-28.6) in patients who received C1 outpatient, 10 months (95% CI 6.67-13.43) in patients discharged after C1, 4 months (95% CI 2.40-6.40) in the C1-C2 continuous hospitalization group, and 1 month (95% CI 0.61-1.30) in those who only received C1 as shown in Figure 1. Patients discharged after C1 had a significantly longer OS compared to the C1-C2 continuous hospitalization group (p=0.003). There was a trend (p=0.054) towards worse survival in patients who received C1 only compared to patients hospitalized continually from C1-C2. Conclusions: Continued hospitalization from C1 to C2 of HMA therapy led to an extremely poor median survival of 4 months in this cohort, compared to 10 months in patients who were able to be discharged after C1 and receive C2 as an outpatient. Patients who only received a single cycle of HMA did not have a significantly different survival as compared to patients who were continually hospitalized from C1 to C2. While this is a small retrospective series, these data suggest that AML patients still requiring hospitalization at time of C2 of HMA therapy should be re-evaluated for alternative therapeutic approaches including hospice given poorer outcomes. Although this grouping selects for patients who are sicker and unable to leave the hospital, there is apparent lack of significant benefit of continued HMA therapy in the majority of patients while inpatient. The impact on hospital length of stay, unnecessary utilization of healthcare resources, and patient's quality of life should also be considered in these cases. Prospective identification of these patients with a poorer prognosis could lead to better alternatives for therapeutic approaches. Disclosures Kremyanskaya: Incyte, Celgene, Constellation, Protagonist.: Research Funding; La Jolla: Consultancy. Navada:Onconova Therapeutics Inc: Research Funding. Mascarenhas:Merus: Research Funding; Pharmaessentia: Consultancy, Membership on an entity's Board of Directors or advisory committees; Merck: Research Funding; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Incyte: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Research Funding; Promedior: Research Funding; Roche: Consultancy, Research Funding; Janssen: Research Funding; CTI Biopharma: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding.

Cytogenetic Features and Clinical Outcomes of Patients With Non-secretory Multiple Myeloma in the Era of Novel Agent Induction Therapy

BackgroundNon-secretory multiple myeloma (NSMM) is a rare subtype of multiple myeloma (MM) characterized by the absence of monoclonal protein in the serum and/or urine. We look at the clinical and cytogenetic features of NSMM in this study. Patients and MethodsThis study evaluates a cohort of 30 patients with newly diagnosed NSMM seen at the Mayo Clinic, Rochester, MN, between 2008 and 2018 and treated with novel agent induction therapies. Survival outcomes were estimated using the Kaplan-Meier method and compared using the log-rank test. ResultsThese patients with NSMM appear to have a large disease burden at diagnosis with a median bone marrow plasma cell percentage of 70% and more than one-half of all patients having Multiple Myeloma International Staging System Stage III disease. There was a higher preponderance for t(11;14) primary cytogenetic abnormality in this NSMM cohort, accounting for more than 50% of the cohort. Finally, the overall survival of this cohort appears to be slightly worse than a matched-control group of newly diagnosed patients with MM with secretory disease. ConclusionsFuture multi-institution studies confirming these above findings on this rare entity are warranted.

PB2125 THE IMPACT OF RVD OR VCD INDUCTION ON RESPONSE 3 MONTH AFTER FIRST LINE AUTOLOGOUS STEM CELL TRANSPLANT IN MULTIPLE MYELOMA. A SINGLE_CENTER RETROSPECTIVE ANALYSIS

Background:The use of triple agent induction therapy before first line high‐dose therapy (HDT) and autologous stem cell transplant (ASCT) in multiple myeloma is now considered standard of care. Cross‐study comparisons show that the combinations of proteasome inhibitors (PIs) and immunomodulatory drugs (IMIDs) have the highest response rates (Malankody Nat Rev Clin Onc 2015).Aims:In recent years there has been a shift in choice of induction therapy from the VCD to the RVD regimen in our region. We have evaluated how this shift has affected depth of response 3 months after ASCT in all patients receiving first line HDT with ASCT in our region from January 1st, 2015, and how frequently our patients needed to change induction regimen, based on choice of first line therapy.MethodsAll patients receiving first line HDT with ASCT for multiple myeloma in our institution in the period from January 1st, 2015 to October 26th, 2019 were evaluated for the final analysis of response 3 months post‐ASCT. The patients received 3‐5 cycles of induction therapy before leukapheresis, HDT (melphalan 200 mg/m2) and ASCT. All patients received a follow‐up consultation in our institution 3 months post‐ASCT, where response was evaluated and recorded according to the IMWG 2016 response criteria.Age, sex, date of ASCT, the presence of high‐risk cytogenetics, ISS stage at diagnosis, choice of induction regimen and response 3 months post‐ASCT was recorded by the primary investigator (Table 1).Results:48.3% (125 patients) received VCD as first‐line induction therapy, while 37.5% (97 patients) received RVD. 12.0% (15 patients) in the VCD group changed induction therapy vs 5.2% (5 patients) in the RVD group. In the RVD group 87.5% (77 patients) achieved ≥VGPR vs 84.5% (93 patients) in the VCD group. In addition, 11.3% in the RVD group (8 patients) achieved PR, while 3.4% (3 patients) had disease progression (PD) 3 months after ASCT. In the VCD group, 13.6% (15 patients) achieved PR, while 1.8% (2 patients) had PD 3 months after ASCT (Table 2, Figure 1). 26% (32 patients) starting VCD induction therapy and 16% (16 patients) starting RVD achieved a response rate &lt;VGPR, or needed to switch induction regimen. We define this as a poor outcome (figure 2).Summary/Conclusion:RVD induction therapy before HDT with ASCT trended toward higher rates of at least VGPR compared to VCD induction (87.5% s 84.5%). The choice of RVD as first line induction therapy necessitated fewer changes of induction regimen due to insufficient response or unacceptable toxicities compared to VCD induction (5.2% vs 12.0%). Fewer patients receiving RVD induction achieved a “poor outcome”: Response &lt;VGPR or need to change induction regimen. These results should be confirmed in larger patient materials, and in prospective studies. Updated data with approximately 30 additional patients, mainly receiving RVD induction, will be presented at the EHA annual meeting if our abstract is selected for presentation.

Clinical and cytogenetic features of nonsecretory multiple myeloma (NSMM) in the era of novel agent induction therapy: The Mayo Clinic experience.

e19519 Background: NSMM is a rare subtype of myeloma that has not been well characterized in the era of novel agent induction therapy. Thus, we evaluated the clinical and cytogenetic features of patients with newly diagnosed NSMM evaluated at our institution. Methods: We evaluated all NSMM patients seen at the Mayo Clinic, Rochester from 2008-2017 based on the absence of a detectable monoclonal protein in their serum and urine electrophoresis and having a concurrent involved serum immunoglobulin light chain of less than 5 mg/dL. Survival analysis was performed by the Kaplan-Meier method and clinical and cytogenetic features were reported descriptively. Results: This cohort consisted of 30 consecutive patients with NSMM with a median age of 62 years (40-79) of which 16 (53%) were male. The median bone marrow plasma cell involvement was 70% (Range: 0 – 100). There were 3/25 (12%) patients who presented with a creatinine of 2 mg/dL or greater and 6/23 (26%) patients who presented with hypercalcemia (11 mg/dL or greater). The ISS classification of this cohort is as follows: Stage 1- 8 (36%) patients, Stage 2- 3 (14%) patients and Stage 3- 11 (50%) patients. There were 6 (21%) out of 28 patients with high risk cytogenetics (either del 17p, t(4;14), t(14;16) or t(14;20). The distribution of primary cytogenetic abnormalities among this cohort was as follows: t(11;14) – 16 (57%), t(4;14) – 1 (4%), trisomies – 6 (21%) and other - 5 (13%). The median overall survival (OS) for patients in this cohort was 59 months (95% CI: 34 – 64). In comparison to a control cohort of newly diagnosed secretory myeloma patients matched for age, gender and year of diagnosis in a 1:2 ratio, the median OS was worse for the NSMM cohort but this was not statistically significant (59 vs. 92 months, p = 0.257). Conclusions: Patients diagnosed with NSMM had a predisposition towards having a t(11;14) primary cytogenetic abnormality. In the era of novel agent induction therapy, they may have a survival outcome that may be worse than newly diagnosed secretory myeloma patients.

Mass Cytometry Identifies Immunomic Shifts in the Bone Marrow Microenvironment of Multiple Myeloma and Light Chain Amyloidosis after Standard of Care First Line Therapies

INTRODUCTION: Traditional cytometry methods have been unable to capture the immense heterogeneity of the tumor immune microenvironment in various malignancies including multiple myeloma (MM). Cytometry by time of flight (CyTOF) can, to some extent, overcome this limitation. However, the computational challenges that come with analyzing these complex datasets in a reproducible manner remain. In this study, using a large cohort of patients, we compare the bone marrow immunomes from patients with MGUS, multiple myeloma (MM), smoldering MM (SMM) and light chain amyloidosis (AL) at diagnosis, after induction therapy with lenalidomide and dexamethasone and after autologous transplant (ASCT). METHODS: We studied a total of 118 cryopreserved samples as follows: 14 healthy donors, 43 AL (27 newly diagnosed-ND, of which 13 with <10% bone marrow plasma cells, 16 matched samples post ASCT), 12 with ND MGUS, 11 with SMM (of which 6 were ND), 14 with ND MM, 13 paired MM samples post induction therapy and 11 paired MM samples post ASCT. Our CyTOF surface staining panel included the following 33 markers: CD45, HLA-DR, CD19, CD3, CD4, CD8, CD14, CCR6, CD11a, Cd123, CCR5, CD7, ICOS, CD25, CD57, CD45RA, CD163, PD-1, PDL-1, CXCR3, CCR4, CCR7, CD28, CTLA4, CD11c, CD56, CD45RO, CD44, CD27, CD138, CD38, CD-127 and CD16. Data processing and analysis was performed using Cytobank. Live cells were identified based on Pt195 and Ir193 staining. Myeloma cells and CD45- cells were excluded and only CD45+ cells were used for subsequent analyses. Single-cell data were downsampled using VisNE, a permutation of t-Distributed Stochastic Neighbor Embedding (tSNE) and clustered using CITRUS (using 10,000 events per sample with a minimum cluster size of 1%). A Significance analysis of microarrays (SAM) analysis was performed to ascertain differences between groups. Significance was inferred for a false discovery rate <1% . All CITRUS analyses were repeated at least 3 times and only clusters found to differ consistently across runs were considered. RESULTS: The proportions of immune subsets identified to vary by CITRUS before and after induction therapy and ASCT for MM and AL are shown in the table. No differences were identified between MGUS, SMM and NDMM. The proportion of a subset (369850) of CD14+/C16- monocytes, a group of cells shown to correlate positively with survival and response to therapy in solid malignancies, increased after induction therapy in MM. Naïve B cells increased dramatically post ASCT in both AL (429918) and MM (369948), consistent with expected immune reconstitution patterns, although a CCR6+ B Cell subset (429940) shown to mediate effective antibody responses, decreased (in grey). A subset (369980) of functionally exhausted (PD1/CTLA4+) central memory (CM) CD4 T cells decreased after induction therapy in MM but recovered early post ASCT whereas a CM CD4+ subset (369986) lacking major activation markers (CD28, CD25) decreased gradually with therapy and post ASCT. A subset (369953) of naïve CD8 T cells shown to be actively recruited in tumor sites (CXCR3+) decreased after ASCT. CD57+ senescent effector memory (EM) CD8 T cells (369962) decreased with induction therapy but recovered post ASCT. EM CD8 T cells associated with long term immune memory (CCR5+, CD127+, cluster 369959), also decreased after ASCT. LIMITATIONS: Include a) No barcoding b) batch effects were difficult to avoid when processing large number of samples c) use of cryopreserved samples d) need for downsampling to cope with the computational burden. The latter could have been one of the reasons we did not identify any differences between MGUS, SMM and MM. At the time of the meeting we will present confirmatory analyses using conceptually different methods of clustering and of performing across group comparisons as well as analyses that do not include downsampling. CONCLUSIONS: Mass cytometry can provide a more granular view of the bone marrow immunome in plasma cell dyscrasias. Novel agent induction therapy can create an immunologically favorable anti-tumor microenvironment although, in some cases, these favorable immunomic shifts are temporarily reversed by ASCT. Confirmatory analyses, baseline immune profiles, comparisons with healthy donors and correlation with other clinically relevant patient characteristics and outcomes will be reported at the meeting. [Display omitted] DisclosuresDispenzieri:Celgene, Takeda, Prothena, Jannsen, Pfizer, Alnylam, GSK: Research Funding. Kumar:Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Membership on an entity's Board of Directors or advisory committees, Research Funding; AbbVie: Membership on an entity's Board of Directors or advisory committees, Research Funding; KITE: Membership on an entity's Board of Directors or advisory committees, Research Funding.

The Impact of RVD or VCD Induction on Response 3 Months after First Line Autologous Transplant in Multiple Myeloma. a Single-Center Retrospective Analysis

Introduction: The use of triple agent induction therapy before first line high-dose therapy (HDT) and autologous stem cell transplant (ASCT) in multiple myeloma is now considered standard of care. While thalidomide/bortezomib/dexamethasone (VTD) is the only induction regimen approved by EMA, both cyclophosphamide/bortezomib/dexamethasone (VCD) and lenalidomide/bortezomib/dexamethasone (RVD) are recommended in the most recent ESMO guidelines (Moreau et al., Annals of Oncology, 2017).Prospective comparisons of VCD and RVD are lacking. Cross-study comparisons show that the combinations of proteasome inhibitors (PIs) and immunomodulatory drugs (IMIDs) have the highest response rates (Malankody Nat Rev Clin Onc 2015).In recent years there has been a shift in choice of induction therapy from the VCD to the RVD regimen in our region. We have evaluated how this shift has affected depth of response 3 months after ASCT in all patients receiving first line HDT with ASCT in our region from January 1st, 2015, and how frequently our patients needed to change induction regimen, based on choice of first line therapy.Methods: All patients receiving first line HDT with ASCT for multiple myeloma in our institution in the period from January 1st, 2015 to March 16th, 2018 were evaluated for the final analysis of response 3 months post-ASCT. The induction regimen was chosen at their local physician´s discretion. The patients received 3-5 cycles of induction therapy before leukapheresis, HDT (melphalan 200mg/m2) and ASCT. All patients received a follow-up consultation in our institution 3 months post-ASCT, where response was evaluated and recorded according to the IMWG 2016 response criteria. No patients had started maintenance therapy at the time of evaluation. Age, sex, date of ASCT, the presence of high-risk cytogenetics, ISS stage at diagnosis, choice of induction regimen and response 3 months post-ASCT was recorded by the primary investigator (Table 1). In case of change of regimen during induction treatment, the reason was recorded. Patients receiving either VCD or RVD as induction therapy, who did not change regimen during induction, were included in the final response analysis.Results: 212 patients received HDT with ASCT in the period. 209 patients were evaluated 3 months after ASCT as of June 21st, 2018. 57.5% (122 patients) received VCD as first-line induction therapy, while 25.9% (55 patients) received RVD. 11.5% (14 patients) in the VCD group changed induction therapy vs 3.6% (2 patients) in the RVD group. Reasons for changing regimen were: not achieving at least a partial response (PR) (n=10), unacceptable toxicity (n=4), lack of documented reason (n=2). In the RVD group, 1 patient died from sepsis 2 weeks post-ASCT, and 1 patient refused to attend the post-ASCT evaluation. Therefore, 108 patients in the VCD group and 51 patients in the RVD group were included in the final response analysis.29 patients could not confirm a complete response (CR) due to lack of bone marrow and/or serum immunofixation at response evaluation. For that reason, patients achieving CR, unconfirmed CR and very good partial response (VGPR) were compounded to a ≥VGPR response grade.In the RVD group 94,1% (48 patients) achieved ≥VGPR vs 85,2% (92 patients) in the VCD group. Similar differences were also present for confirmed CR (25% vs 18%) and unconfirmed CR (44% vs 35%). In addition, 2% in the RVD group (1 patient) achieved PR, while 3.9% (2 patients) had disease progression (PD) 3 months after ASCT. In the VCD group, 13.0% (14 patients) achieved PR, while 1.8% (2 patients) had PD 3 months after ASCT (Table 2, Figure 1).Discussion: RVD induction therapy before HDT with ASCT yielded higher rates of at least VGPR compared to VCD induction (85,2% s 94,1%). The choice of RVD as first line induction therapy necessitated fewer changes of induction regimen due to insufficient response or unacceptable toxicities compared to VCD induction (3,6% vs 11,5%). The differences were not statistically significant, possibly because of too few patients. Still, our results support the trend in our region of choosing RVD as first-line induction for transplant-eligible patients. These results should be confirmed in larger patient materials, and in prospective studies.Updated data with approximately 35 additional patients, mainly receiving RVD induction, will be presented at the ASH annual meeting if our abstract is selected for presentation. [Display omitted] DisclosuresMoksnes:Shire: Consultancy. Schjesvold:Amgen: Consultancy, Honoraria, Research Funding; Celgene: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; Bristol Myers Squibb: Consultancy; Bayer: Consultancy; Janssen: Consultancy, Honoraria, Research Funding; Oncopeptides: Consultancy; Abbvie: Honoraria; Adaptive: Consultancy; Novartis: Honoraria.