ALBERT

Description: Introduction: Lenalidomide (L) is a compound in a new group of drugs called ImiDs® which have Immunomodulatory properties and with anti-tumor activity reported in multiple myeloma and MDS. Although the exact mechanism of action of L is unknown, they are reported to affect the tumor microenvironment through modulation of critical cytokines such as TNF-a, VEGF and IL-6. These cytokines also play an important role in pathogenesis of CLL. Based on these properties we have investigated and previously reported on the anti-leukemic activity of thalidomide in CLL. We subsequently conducted a phase II study with L, to evaluate its clinical activity in pts with relapse (rel) or refractory (ref) CLL. Here we present the results of this study. Patients and Methods: CLL pts with rel or ref disease were eligible. L was given at 25mg PO QD x 21 days followed by 7 days rest on a 28 day cycle. Absolute lymphocyte counts (ALC) were measured at Day 0, 7 and 30. Response was assessed at day 30 and monthly thereafter using the NCI-WG 1996 criteria. Pts with stable disease (SD) or better response were continued on therapy for a maximum of 12 months while those with progressive disease (PD) were to receive rituximab (R) (375mg/m2) added to L. Pts were considered evaluable for response if they completed at least 2 months of treatment. Target enrollment is 29 patients. Results: Twenty nine pts, median age of 64 years (range: 47–75) were enrolled. All pts are available for toxicity and 17 out of 29 pts available for response evaluation. Three pts on treatment are too early for response assessment while 9 pts are off study (2 withdrew consent and 5 got 〈 2 months of therapy due to toxicity). Response is reported based on evaluable pts. Complete remission (CR) was noted in 2/17 (11.7%) pts while partial remission (PR) was noted in 9/17 (52.9%) pts. Additional 5/17 (29.4%) pts, currently on treatment, achieved stable disease (SD). ORR (CR+PR) in the intent to treat population is 42.3% (11/26, excluding pts currently too early for response assessment). To date only 1 pt has PD after 3 months of L and is on LR per protocol. Toxicity: Flare reaction (tender swelling of lymph nodes and/or rash) was the most common SE noted in almost all pts. Other important SE were tumor lysis syndrome (n=2); grade 3/4 hematologic toxicities (n=7) and febrile neutropenia (n=3). Conclusion: This is the first study to report the clinical activity of L in pts with CLL. Our findings are encouraging and provide evidence of the anti-CLL activity of L. Although some of the pts did achieve a CR, longer follow-up will determine the durability of responses noted to date. Update results of this study along with toxicity profile of L in CLL will be presented at the meeting.

Description: An ex vivo trial utilizing photopheresis with Benzoporphyrin Derivative as the photoactive compound, identified the minimum energy levels of light and concentrations of BPD that eradicated both cell-free and cell-associated HIV-1 infectivity without destroying the virus particles or infected leukocytes. Leukocytes remained viable with altered chemokine/cytokine expression. Apoptosis was induced in a minority of CD4 but not CD8 positive cells with a statistically significant increase in cytolytic T-cell activity. In the 24 week clinical trial in seven HIV-1 infected patients. Three who had rapidly rising viral loads prior to initiating therapy stabilized. Two had a (sustained) greater than .5 log decrement and 5 had stable plasma viral loads (less than a .5 log increment or decrement) with varied effects on absolute CD4 and CD8 positive lymphocytes counts. One achieved a greater than 1 log decrement in HIV-1 plasma viral load and undetectable in vivo cell-free and cell-associated HIV-1 infectivity with an increased in vitro lymphocyte mitogen stimulation index. Under amended protocol 5 additional 12 month courses were administered to three additional patients and two of the previous enrollees. Area under the curve for viral load showed a significant decrease from pre to post therapy (p 0.007). No associated toxicities observed.

Description: Introduction: Prophylactic platelet transfusions are often given when a predetermined platelet count is reached and the amount given is that necessary to achieve a desired post count. This method of transfusion ignores the question of whether the patient receives increased benefit from transfusion when more than one unit is given. To determine what effect this practice has had on transfusion outcome and platelet utilization, we have reviewed 5 years of platelet transfusion data to look specifically at transfusion events when more than one single donor platelet was given during a 24 hour period. Methods: Transfusion data was obtained from that used for utilization review 2002 –2006. The data was sorted to identify records indicating that 2 or more units of apheresis platelets were received in a 24 hour period. This information was further selected to include only those with hematologic diseases. The platelet counts identified for inclusion were the counts prior to the release of the first unit given during the day and the first count after the release of the last unit. The change in the platelet count for the number of units was recorded and averaged for each unit increment for each record. Statistical analysis was performed and was not statistically significant. Results For the 5 year period, 86% of all platelet transfusions at our institution were given to patients with hematologic diseases and 27% of these were given as 2, 3, or 4 units within a 24 hour period. 716 records had 2377 days with multiple transfusions; 1802, 428, and 147 episodes of 2, 3, and 4 units respectively. The increase in platelet count for a single unit transfusion at our institution averages 32.3 ×109/L. The platelet increments for 2, 3, and 4 units showed no statistical increase from this number or each other. There is no trend for the final platelet count to be greater when more units are given. These results do not take patient condition or the use of specialized products into consideration. Discussion: Our experience suggests that transfusions of multiple platelet units may not have a greater impact on platelet increments than that when fewer units are transfused. To fully understand this data and its potential impact on patient care, further subgroup analysis within the platelet increments and correlation with patient condition and the prescribed transfusion parameters is needed. Figure Figure

Description: In the past, the most common initial combination chemotherapy regimen used by most oncologists to treat B-cell lymphoma was the CHOP regimen. Although doxorubicin (DOX) is a major component of CHOP, it is associated with myelosuppression, alopecia, and potential cardiotoxicity. In vitro data has demonstrated synergistic activity between rituximab and certain drugs, including DOX. Because of D’s unique liposomal encapsulation, delivery, and toxicity profile, it may prove to be a more effective, less toxic anthracycline to combine with R. A formal Phase I/II trial to evaluate the safety and efficacy of R+D in pts with relapsing B-cell lymphoma was undertaken. R (375 mg/m2/dose) was given on day 1 and D (30 mg/m2/dose) on day 3 on q 21 day cycles for 6 cycles. Thirteen pts have completed therapy to date: 9F, 4M; Follicular lymphoma, grade 1 (n=6), grade 2 (n=1), grade 3 (n=3), DLBCL (n=3); med age = 63 (38–78); median number of prior Rx’s = 3 (range 1–8); prior anthracycline exposure (n=8). Overall, the combination of R + D was well-tolerated. Transient grade 3 cytopenias were noted in 3 pts with limited bone marrow reserve and grade 3 palmar/plantar erythrodysesthesia seen in 2 pts. All 13 pts completed the planned 6 courses of Rx. Objective responses were seen in 85% (11 of 13 pts), including 54% CR, 31% PR. Median time-to-progression has not been reached at 7+ months (range 4.5+ to 19+ months). No cardiac toxicity was seen and comparison of pre-Rx to post-Rx LVEF remained unchanged in 9, increased in 2, and decreased in 2 (yet still remaining 〉 50%). D + R immunochemotherapy is a well-tolerated, unique, non-cardiotoxic, and apparently effective salvage therapy for relapsed B-cell lymphoma. The study will continue until accrual of 42 pts has been reached.

Description: Despite the improved outcome in patients with DLBCL treated with rituximab (R) in combination with systemic chemotherapy (R + chemotherapy), a significant number of patients either relapse or fail to respond as a consequence of resistant disease. HDC and ASCT is the best therapeutic strategy to rescue relapsed/refractory DLBCL. It has been postulated that R+chemotherapy may lead to the selection of highly resistant lymphoma cells diminishing the clinical benefit of HDC and ASCT. Preliminary data from the CORAL study (Gisselbrecht et al Blood2007; 11:517a) suggest that overall response rates (ORR) and 2-year event free survival (EFS) are lower in R+chemotherapy relapsed/ refractory DLBCL when compared to DLBCL treated with chemotherapy alone. However the second randomization of this study to observation versus R-maintenance may affect the interpretation of the data. We retrospectively studied the difference in the outcomes of relapsed/refractory DLBCL patients following HDC and ASCT according to the front line therapy utilized (R+chemotherapy versus chemotherapy). Using the Roswell Park Cancer Institute (RPCI) Tumor Registry and the RPCI Blood and Marrow Transplant (BMT) Database we identified 130 patients with relapsed/refractory NHL who underwent for HDC + ASCT from 1991 to 2008. After excluding patients with a diagnosis other than B-cell DLBCL (patients with transformed NHL were excluded) and those patients receiving allo-BMT after progression from ASCT, the analysis included 63 refractory/ relapsed DLBCL. Demographic characteristics, clinical data, treatment history in the front line and salvage setting were collected. In addition response to salvage therapy and disease status at day +100 from ASCT was recorded for each subject. Progression free and overall survival were calculated from ASCT. Differences in clinical outcomes between patients receiving R as part of first line or salvage treatment and those treated with chemotherapy alone were evaluated by multivariate analysis, adjusting for significant univariate predictors of survival. The patient cohort included 34 males and 29 females with median age of 46 yrs (14.4 to 69.4). Two-thirds of the patients had advance disease and the majority had a Karnofsky performance status (KPS) of 80–100% at diagnosis. R+chemotherapy was given in the front line setting to 25 pts and while 38 received chemotherapy alone. In the salvage setting, 35 pts (55%) received R+chemotherapy. Most relapses (44 pts) occurred within 6 months of completion of front line therapy (17 pts with vs. 27 pts without R). The use of R in the front line setting was associated with significantly higher response rates (PR + CR) to salvage chemotherapy (P = 0.036) and better disease control on day +100 post-ASCT (P = 0.016) when compared to chemotherapy alone. In our cohort, there have been 32 deaths, 23 in chemotherapy treated DLBCL in contrast to 9 deaths in R+chemotherapy treated patients There was a significantly higher response rate post-ASCT for R+chemotherapy treated (as front-line or salvage) DLBCL versus chemotherapy alone (P = 0.007). A multivariate analysis demonstrated that achieving a CR pre-ASCT was the most important predictor of post-ASCT progression free and overall survival . In summary, our data suggest that the use of R + chemotherapy during frontline therapy and in the salvage setting yields better disease control and less incidence of chemo-resistant disease at the time of BMT. Applying the natural selection theory, the use of R+chemotherapy is expected to result in the development of resistant lymphomas. The length of time and the amount of R therapy that will render lymphoma cells resistant to chemo-immunotherapy remain to be determined. Standard doses of R (6 to 8 doses) do not appear to affect response to salvage therapy or autologous BMT outcomes. In our single institution analysis over the last 18 years, it appears that HDC + ASCT is an effective and viable option for patients with R +/− chemotherapy relapsed/refractory DLBCL.

Description: Background: Tumor microenvironment (ME) plays an important role in MM. It is associated with disease progression, metastasis, and resistance to therapy. Therefore, targeting the ME and the tumor cell simultaneously may be an effective way to overcome resistance in pts with rel/ref MM. Aim: Orlowski et al reported improved anti-tumor responses when bortezomib (V) was combined with doxil (D) in pts with hematologic malignancies. We investigated clinically, this approach i.e., targeting the MM cell as well as its ME, using a combination of V, D and low-dose thalidomide (T) as salvage therapy for pts with rel/ref MM. Here we report the final results along with survival data of this phase II study. Methods: All pts with rel/ref disease were eligible for this study. V was given at 1.3mg/m2 (D1,4,15,18) and D at 20mg/m2 (D1,15) every 4 weeks with daily T (200 mg) for 4–6 cycles. SWOG criterion was used to assess response. Low-dose coumadin (1–2 mg po qd) was used for prevention of venous thromboembolism (VTE). Results: Twenty three pts (9M, 14F; median age −57 , range 43–79 yrs; 21MM, 2 WM) have been enrolled. All pts had Stage III disease, median b2M was 4.2 and median number of prior therapies were 5(range 1–6). Prior therapies included stem cell transplant(SCT) in (41%), T (41%), adriamycin(A) (65%) steroids (82%) and velcade (12%). 74% had refractory disease. Seventeen pts have completed at least 1 cyc and are available for toxicity and response evaluation. One pt died of sepsis prior to completing 1 cyc and 1 pt with PR was taken off study for non-compliance after 1 cyc. ORR was with 65%(CR+PR) with 23% CR all of whom were IFE negative. The Median Progression Free survival was 10.9 months with an median overall survival of 15.7 months. Toxicity: 2 pts developed Gr. II plantar-palmar erythrodysthesia (PPE) and 1 had Gr. III cellulitis. No VTE was noted. No significant non-hematologic Gr. III/IV toxicity were seen. Despite prior exposure to anthracycle, we did not noted any cardiotoxicity with D.No significant neuropathy was noted. Conclusions: Pt with rel/ref MM usually have aggressive disease with paucity of effective regimens. VDT is an effective salvage regimen. Final results show high response rates with 22% of the patients achieving complete (IFE−) remissions. Responses were noted regardless of type of prior therapy. VDT could be safely given in patients with renal failure/insufficiency. Venous Thromboembolism (VTE) does not appear to be a problem with low dose coumadin prophylaxis. Final results of this phase II study will be presented at the 48 th annual ASH meeting.

Description: Abstract 1322 Poster Board I-344 Background Veltuzumab, a 2nd-generation humanized anti-CD20 monoclonal antibody with structure-function differences from rituximab, has demonstrated clinical activity at low doses in non-Hodgkin's lymphoma (Morschhauser et al., J Clin Oncol, 2009; 27:3346-53). Since chimeric anti-CD20 rituximab is therapeutically active in ITP, we conducted a clinical trial of low-dose veltuzumab in ITP, initially administered by intravenous (IV) infusion, but following development of a high-concentration formulation, now administered by subcutaneous (SC) injection. Methods A multicenter, phase I/II study was undertaken to evaluate the safety and tolerability of low-dose veltuzumab in adults who had ITP for at least 6 months, had failed ≥1 standard therapy, and presented with platelets ≤30K/≤L, but without major bleeding. All patients received 2 doses of veltuzumab 2 weeks apart (without steroids) and were followed for up to 12 weeks, with responding patients continuing in long-term follow-up. Efficacy was assessed by an increase in platelet count with confirmation at least 1 week apart. Responses were classified as complete (CR, 〉150K/μL), partial (PR, 50-150K/μL), or minor (MR, 30-50K/μL). Adverse events and safety laboratories were evaluated using NCI CTC v3 toxicity grades. Other evaluations included circulating B-cell levels (CD19), veltuzumab serum levels, and human anti-veltuzumab antibody (HAHA) titers. Results The study has enrolled 25 patients (7M/18F, 21-92 years old, 5 post-splenectomy) with 7 receiving 2 IV veltuzumab doses at 80 (N=3), 120 (N=3), or 200 mg (N=1), and 10 receiving 2 SC doses at 80 (N=3), 160 (N=4), or 320 mg (N=3) during the completed Phase I portion of the study. The Phase II portion is now underway with 8 additional patients having received 2 SC veltuzumab doses at 320 mg. The 25 patients had a median duration of ITP of 1.8 years (range 0.2 - 20) with previous treatments including steroids (N=24), IVIG/anti-D (N=15), azathioprine/danazol (N=7), rituximab (N=5), TPO-R agonists (N=3) and vincristine/Doxil (N=2). One patient had a Grade 3 infusion reaction after receiving ∼100 mg veltuzumab at first IV dose. Otherwise veltuzumab was well tolerated with a limited number of Grade 1 infusion/injection reactions and no other safety issues. B cells were depleted rapidly with both IV and SC dosing with recovery times yet to be determined. At 80 and 120 mg x 2, IV veltuzumab achieved expected serum levels (mean Cmax 20.3 and 46.0 μg/mL, respectively) with a mean serum half-life of ∼1 week after last dose. SC veltuzumab had slower release over several days with lower serum levels, but comparable availability/exposure. Two patients developed low-level HAHA titers of uncertain clinical significance. Of 21 patients now with post-treatment response assessments, 13 (62%) achieved an objective response (CR+PR+MR), including 6 (29%) CRs. Responses, including CRs, occurred with both SC and IV administrations, and across all dose levels, with the highest OR (CR) rate of 100% (60%) seen in patients with more recently diagnosed ITP (≤1 year), albeit in small numbers of patients (N=5). Of 6 CRs, 5 are still continuing with a current median duration of response of 9 months (2.5 - 15 mo.) Conclusions Low-dose veltuzumab (2 doses, 2 weeks apart) demonstrates promising activity in relapsed ITP, including durable complete responses. Compared to IV infusions, subcutaneous injections offer practical benefits to both patients and the healthcare system, and the study is continuing to provide additional/confirmatory data for further clinical development of SC veltuzumab in ITP. Disclosures Saleh: Immunomedics: Research Funding. Off Label Use: veltuzumab, an investigational anti-CD20 antibody in clinical studies. Liebman:Immunomedics: Research Funding. Bernstein:Immunomedics: Research Funding. Negrea:Immunomedics: Research Funding. Bussel:Immunomedics: Research Funding. Onyegbula:Immunomedics: Research Funding. Farber:Immunomedics: Research Funding. Abassi:Immunomedics: Research Funding. Cosgriff:Immunomedics: Research Funding. Pennington:Immunomedics: Research Funding. Horne:Immunomedics: Employment. Teoh:Immunomedics: Employment. Gomaa:Immunomedics: Employment. Wegener:Immunomedics: Employment. Goldenberg:Immunomedics: Employment, Equity Ownership.

Description: Introduction: Lenalidomide (L) is an immunomodulatory agent (IMiD®), recently approved for treatment of patients (pts) with previously treated multiple myeloma and del 5q- MDS. Its antitumor effects are reported to be mediated at least in part through modulation of both the cytokine and the immune cellular tumor microenvironment. Clinical efficacy of L in pts with B-CLL has not been investigated previously. In a phase II clinical study, we examined the antileukemic effects of L in pts with relapse (rel) or refractory (ref) B-CLL. Patients and Methods: CLL pts with rel or ref disease were eligible. L was given at 25mg PO QD from days 1–21 of 28-day cycle. Response was assessed every month using the NCI-WG 1996 criteria. Treatment with L was continued until progressive disease (PD) or molecular complete response (CR). Pts with PD received rituximab (R) (375mg/m2) with L. Target enrollment was 45 patients. Results: Forty-five pts, median age of 64 years (range: 42–75) were enrolled. Advance stage disease was noted in 64%, elevated B2M in 24% and fludarabine refractory disease in 51% of the pts. Pts had a median of 3 prior therapies (range 1–10). All pts are evaluable for toxicity. Thrombocytopenia and neutropenia were the most common hematologic toxicity while fatigue and flare reaction (sudden, tender enlargement of lymph node, liver and/or spleen, with or without rash, low grade fever and/or increase in white blood counts) were the most common non-hematologic complications. Two patients experience reversible tumor lysis syndrome. On an intent-to-treat analysis, overall response rate was 42% with complete remission in 9% (n=4) and partial remission in 33% (n=15) of the pts. Molecular complete response (determined by PCR) was noted in 3 pts. Twelve pts were inevaluable (unable to complete 2 treatment cycles; either for toxicity or consent withdrawal) 4 are too early for response evaluation. Response rate among evaluable patients was 65.5% (19/29). To date only 2 pts have required the addition of R to L due to PD. Both have achieved a PR with combination therapy. Correlative studies: we evaluated baseline T and NK cell repertoire, modulation of cytokines (VEGF, IL-10, IL-6, TNF-alpha) as well as modulation of gene expression profiles before and after treatment with L, this data will be presented at the meeting. Conclusion: L is clinically active in pts with rel/ref CLL. CR’s, as well as, molecular CR determined by PCR were achieved with single agent L. Interestingly, in pts who developed resistance to L alone, addition of R resulted in a clinical response. These results are exciting and warrant further investigation of L in CLL pts. Final results of this study will be presented at the meeting.

Description: Background: Aberrant over-expression of BCL-2 is a poor prognostic factor in patients with DLBCL. t(14;18) (q32;q21) results in transcription of the anti-apoptotic BCL-2 protein. In vitro studies have shown that rituximab induces an IL-10 dependent down regulation of BCL-2 and sensitizes cancer cells to the effect of chemotherapy agents. It has been reported that the addition of rituximab to chemotherapy has eliminated the prognostic significance of BCL-2 over-expression in DLBCL. However limited information is available regarding the prognostic significance of BCL-2 over-expression driven by t(14;18) following rituximab/chemoimmunotherapy. To this end we correlate the levels of Bcl-2 expression and response to front-line treatment in patients with primary refractory DLBCL (PR-DLBCL). Methods: A single-institution retrospective data analysis was done to identify all DLBCL patients treated between 1/1/02 and 12/31/06. Patients with PR-DLBCL, as defined by residual disease at the end of primary treatment or disease relapse within 6 months of completing it were identified. Patient demograpics, international prognostic index (IPI) score, treatments administered, outcome and Bcl-2 status were reviewed. Bcl-2 translocation was studied by a nested PCR-based assay of peripheral blood samples. The test is reproducibly sensitive to a detection level of 1:105 and reported the presence or absence of t(14;18) as a positive or negative result. BCL-2 protein expression in tissue was studied with immunohistochemistry (IHC). Results: A total of 246 patients with DLBCL were identified. Of these, 27 (11%) qualified as PR-DLBCL. Median age at diagnosis was 56 years (range 16–84). Thirteen (48%) were females and 14 (52%) were males. IPI score was 0 in 2 (7.5%), 1 in 9 (33.3%), 2 in 6 (22.2%), 3 in 4 (14.8%) and 4 in 6 (22.2%) patients. Disease was labeled ‘bulky’ (〉 5 cm lymphadenopathy) in 11 (41%) patients at the time of diagnosis. Twenty four (89%) patients received an initial rituximab-containing regimen and radiation therapy was administered to 13 (48%) patients. Median overall survival for all the 27 patients was 570 days (range 151–1437). Ten (37%) patients received peripheral blood stem cell transplantation during the course of their disease. At the time of analysis, 14 (52%) patients were alive and of these, 7 (50%) had persistent disease, while the other 7 (50%) were disease-free. t(14;18) data was available on 18 of these 27 patients and all were negative for the translocation. All of these 18 patients had received rituximab-containing initial therapy. Of these 18 patients, IHC for BCL-2 expression was available for 8 (44%), and was positive in all 8 patients. Conclusions: Bcl-2 over-expression is observed in a significant number of patients with primary rituximab/chemotherapy refractory DLBCL. In our selected group of patients, the t(14;18) does not appear to play a role in the expression of BCL-2, suggesting the existence of additional mechanisms responsible for BCL-2 upregulation. In addition, 70% of our PR-DLBCL patients did not express BCL-2, leading to the hypothesis that various regulatory proteins such as other members of the BH3 domain family play a role in determining rituximab/chemotherapy sensitivity.

Description: Abstract 3302 Background: Subcutaneous (SC) injections of veltuzumab, a 2nd-generation humanized anti-CD20 monoclonal antibody with structure-function differences from rituximab, may offer potential benefits to both patients and the healthcare system. In non-Hodgkin's lymphoma, SC veltuzumab was well tolerated and demonstrated activity (Negrea et al., Haematologica, 96:567–73, 2011) comparable to that demonstrated earlier with low veltuzumab doses delivered intravenously (Morschhauser et al., J Clin Oncol, 2009;27:3346–53). Since this route of administration may also be effective and particularly convenient for treating autoimmune disease, a clinical study of SC veltuzumab was undertaken in immune thrombocytopenia (ITP). Methods: A multicenter, phase I/II study was conducted to evaluate veltuzumab in adults with primary ITP who failed ≥1 standard therapy and presented with platelets ≤30K/μL, but without major bleeding. All patients received 2 doses of veltuzumab 2 weeks apart (without steroids or other premedications required). Veltuzumab was initially administered IV, but then by SC injection after a higher concentration formulation became available. By recent international working group categories, efficacy was evaluated separately for patients with newly-diagnosed or persistent disease (≤1 year duration) compared to patients with chronic disease (〉1 year), with best responses (on at least 2 occasions, one week apart) classified as complete (CR, 〉150K/μL), partial (PR, 50–150K/μL), or minor (MR, 30–50K/μL). Adverse events (AEs) and safety laboratories were evaluated by NCI CTC v3 toxicity grades. Other evaluations included circulating B-cell levels (CD19), veltuzumab serum levels, and human anti-veltuzumab antibody (HAHA) titers. Results: A total of 41 patients were entered in this study, with 7 patients receiving 2 IV veltuzumab doses of 80 (N=3), 120 (N=3), or 200 mg (N=1), and 34 receiving 2 SC doses of 80 (N=9), 160 (N=10), or 320 mg (N=15). One patient had a Grade 3 infusion reaction after receiving ∼100 mg veltuzumab at first IV dose. Otherwise veltuzumab was well tolerated with a limited number of AEs (All NCI CTC v3.0 Grade 1–2 transient infusion/injection reactions) and no other safety issues. ORs and CRs occurred with both SC and IV administrations, and across all dose levels. Of 9 patients (6 female/3 male; median 54-years old) with ITP ≤1 year and treated with steroids and/or immunoglobulins, 7 (78%) achieved an objective response (OR: CR+PR+MR), including 3 (33%) CRs. Of 32 patients (19 female/13 male; median 51-years old) with ITP 〉 1 year, (47% 5 – 31 years) and additional therapies [splenectomy (N=8), azathioprine (N=9), rituximab (N=6), tpo-receptor agonists (N=5), chemotherapy (N=5)], 19 (59%) still achieved ORs, including CRs in 4 (13%) patients with ITP for 1.4, 2.0, 2.4 and 25 years. Of 7 CRs, the median relapse-free survival was 1.2 years, and 3 still continue 1.8 – 3.5 years after treatment. Most PRs and MRs relapsed by 6 months. However, of 6 such patients who were then retreated, 4 patients achieved responses comparable to their initial response, while another patient (with a 31-year history of ITP) achieved a CR after receiving veltuzumab in combination with prednisone. With both IV and SC dosing, and at all doses, B cells were depleted rapidly after the first administration of veltuzumab, with recovery starting 12 to 16 weeks after treatment. Compared to IV dosing, SC veltuzumab had slower release over several days with lower serum levels, but approximately comparable availability/exposure. Four patients developed low-level HAHA titers of uncertain clinical significance. Conclusions: Low-dose SC veltuzumab was convenient, well tolerated and with promising activity in relapsed ITP. With only 2 SC doses, patients with limited disease duration of ≤1 year achieved high rates of objective responses [78%], including 33% durable CR's. In patients with long-standing disease (47% with ITP for 5 – 31 years) and who were often heavily pretreated, CRs occurred less frequently, but there was still activity [59% ORs]. Higher doses and extended dosing SC regimens may be more effective in this more refractory population. Disclosures: Liebman: Immunomedics: Research Funding. Saleh:Immunomedics: Research Funding. Bussel:Immunomedics: Research Funding. Bernstein:Immunomedics: Research Funding. Negrea:Immunomedics: Research Funding. Onyegbula:Immunomedics: Research Funding. Farber:Immunomedics: Research Funding. Horne:Immunomedics: Employment. Wegener:Immunomedics: Employment. Goldenberg:Immunomedics, Inc.: Consultancy, Employment, Equity Ownership, Honoraria, Membership on an entity's Board of Directors or advisory committees, Patents & Royalties, Research Funding.