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Background Therapeutic advancements and deeper understanding of disease biology have helped improve the outcomes of multiple myeloma (MM). However, there is no consensus regarding the optimal management of patients whose disease becomes refractory to the three main class of drugs [proteasome inhibitors (PI), immunomodulatory drug (IMiD), and monoclonal antibodies (mab)] or among those presenting with complications secondary to rapidly progressive disease. While chimeric antigen receptor T-cell (CAR-T) and bispecific T-cell engagers have yielded high rates of durable responses, access to these therapies in clinical trials is often hindered by high disease burden compromising eligibility. We evaluated the use of a combination of cytotoxic agents (cyclophosphamide, doxorubicin, vincristine, and dexamethasone; mHyperCVAD) in this challenging population. Methods This is a retrospective, single center study evaluating the safety/tolerability and efficacy of mHyperCVAD in relapsed and refractory MM (RRMM). The regimen consists of cyclophosphamide 300 mg/m2 IV every 12 hours on D1-4 (total 2400 mg/m2), vincristine 0.4 mg/day IV continuous infusion D1-4 (total 1.6 mg), doxorubicin 9 mg/m2/day IV continuous infusion D1-4 hours (total 36 mg/m2) and dexamethasone 40 mg PO daily D1-4. Adult patients with RRMM were included if they received ≥1 cycle of mHyperCVAD between 2019-2021. Patients with primary plasma cell leukemia were excluded. Response was assessed by International Myeloma Working Group Uniform Criteria. Overall response rate (ORR) and disease control rate (DCR) were defined as ≥ partial response and ≥ stable disease, respectively. Patients were censored for progression free survival (PFS) at the last follow-up date if neither progression nor death occurred. All patients received growth factors, and infectious disease prophylaxis per institutional standard. Toxicities were graded using CTCAE v5.0 up to 30 days post therapy. Results Between 1/2019 and 7/2021, 39 patients met the inclusion criteria and received 44 courses of mHyperCVAD (four patients received mHyperCVAD at more than one timepoint). The median age was 54 years (range 32-71), 56% male. 36% patient had ISS stage III disease and 56% had high risk disease [t(4;14), t(14;16), del17p, +1q]. The median lines of therapy prior to mHyperCVAD were 3 (range 1-12) with 93% triple class refractory (refractory to PI, IMID and mab) and 64% penta-refractory (refractory to 2 PI, 2 IMiDs and mab) and 76% had received a prior autologous transplant. The median number of mHyperCVAD cycles per course was 1 (range 1-8). Baseline characteristics are summarized in Table. Eleven courses (25%) were administered as bridge after lymphocyte collection for the manufacture of CAR-T cells and prior to lymphodepletion chemotherapy (100% triple class refractory and 91% penta-refractory) with ORR 18% and DCR 72%. Thirty-three courses (75%) were used as salvage for rapid disease control. The most common toxicities with mHyperCVAD were hematologic (65% grade 3/4 toxicities) with 20% incidence of febrile neutropenia. Four patients died during mHyperCVAD therapy due to rapidly progressive disease and one patient died due to sepsis. For the entire cohort, the ORR is 50% (≥VGPR 30%) with a DCR 82%. Additionally, 39% could proceed with experimental CAR-T cells and/or bispecific T cell engagers. The median progression free survival is 3.6 months, and the median overall survival is 8 months from start of mHyperCVAD with 10.5 months median follow up. The most common cause of death was progressive disease (39%). Conclusion mHyperCVAD is an efficacious cytotoxic chemotherapy regimen which can achieve rapid disease control allowing patients an opportunity to proceed with additional therapies, including investigational agents on clinical trials. It can also be used as an effective bridging strategy among heavily treated, triple class and penta-refractory MM awaiting manufacturing of CAR-T cells with manageable and expected toxicities. Figure 1 Figure 1. Disclosures Giri: PackHealth: Research Funding; CareVive: Honoraria, Research Funding. Costa: Karyopharm: Consultancy, Honoraria; Amgen: Consultancy, Honoraria, Research Funding, Speakers Bureau; Janssen: Consultancy, Honoraria, Research Funding; BMS: Consultancy, Honoraria, Research Funding; Pfizer: Consultancy, Honoraria; Sanofi: Consultancy, Honoraria, Speakers Bureau.

Background : This study aimed to determine the effect of Hyper-Cyclophosphamide, Vincristine, Adriamycin, and Dexamethasone (CVAD) in the treatment of acute lymphoblastic leukemia (ALL) patients and remission duration. Materials and Methods: During a cross-sectional study in the Seyed Al-Shohada Hospital in Isfahan, patients with ALL who were admitted and treated from 2011 to 2015 because of the risk of ALL were selected and through the records investigation, demographic information, disease information, treatment, remission duration, current status, and duration of survival were collected in the form of data and are sick after going into remission, including the duration and recurrence remission survival time in treatment were analyzed and consequence, whether the patient is going into remission, remission and relapse and survival time based on the duration of treatment were analyzed. Results : Of the 62 patients, 13 patients after starting of treatment did not go to remission and died, but 49 patients (79%) went into complete remission. 21 of them of Hyper-CVAD group and 28 patients of classical treatment group (75/7% vs. 84%), but the difference was not significant ( P = 0.43). Of the 48 patients who had a complete remission with the treatment regimen, ten patients relapsed after treatment with two of them of Hyper-CVAD group and eight patients were in the classical treatment group (9/5% vs. 29/6%), and the difference between the two groups was significant ( P = 0.015). Conclusion: Hyper-CVAD regimen resulted in increased survival time of patients with ALL and less disease recurrence and therefore contraindications for use if the existing rules, and under the supervision of treatment, can be used.

The increasing complexity of cancer chemotherapy heightens the requirement that pharmacists be familiar with these highly toxic agents. This column will review various issues related to preparation, dispensing, and administration of cancer chemotherapy. It will also serve as a review of various agents, both commercially available and investigational, used to treat malignant diseases. Questions or suggestions for topics should be addressed to Dominic

8563 Background: The R-CHOP regimen has become the standard of care for treatment of patients with aggressive B-cell lymphomas. Pegylated liposomal doxorubicin (PLD) has an improved pharmacokinetic...

17506 Background: The majority of patients (pts) with diffuse large B-cell lymphoma (DLBCL) are elderly and may have limited tolerance to intense chemotherapy. Myocet has an improved therapeutic index in comparison to doxorubicin, resulting in less myelosuppresion, lower GI toxicity and reduced risk of cardiotoxicity. The aim of this study was to assess the efficacy and safety of the R-CHOP modified by replacing doxorubicin with Myocet (R-COMP) in pts ≥ 60 years with newly diagnosed, advanced DLBCL. Methods: Sample size was defined with the level of no interest P0 = 40% of CRs and the level of interest P1 = 60% of CRs. After assessment of the first 25 evaluable pts accrual continued to 75 pts, sample size estimated to include 66 evaluable pts. R-COMP regimen: d1 every 3 wks Myocet 50 mg/m2, cyclophosphamide 750 mg/m2, vincristine 1.4 mg/m2 (max. 2 mg), rituximab 375 mg/m2 (d3 C1, d1 thereafter) and prednisone 100 mg/d d1–5. After 3 cycles pts with an objective response received 5 additional cycles. Results: Between Oct 2002 and Apr 2005, 75 pts were registered. This analysis includes the first 51 evaluable pts: median age was 71 (60–83); 56% of pts had an intermediate or high risk IPI score (≥ 3); median LVEF at baseline was 60% (50–89). Relative dose intensity was 89.8%. Median treatment of 8 cycles (1–8). Thirty-four pts (67%) achieved CR (95% CI = 51, 5–79,3) and 10 pts (20%) PR; Five percent of cycles were delayed and 9% were dose reduced due to toxicity. Toxicity: Grade (G) 3–4 neutropenia in 22% of cycles (52% of pts), febrile neutropenia in 3% of cycles (12% of pts), G 3–4 thrombocytopenia in 2 cycles, one episode of neutropenic sepsis, mucositis and related infections in 1% of the cycles each. Median final LVEF was 60% (40–79). Four pts were withdrawn due to decrease in LVEF. One pt had acute pulmonary oedema (considered related to the drug in absence of other reasons). No pts had congestive heart failure related to study drug. Conclusions: The R-COMP regimen is a well-tolerated and effective treatment for aggressive NHL in elderly pts. Both, the general tolerability and the low incidence of cardiac events warrants further studies in order to confirm the clinical benefit of R-COMP in elderly population. [Table: see text]

Phase II study of cyclophosphamide, vincristine and D.T.I.C. ± B.C.G. in the treatment of malignant melanoma. M. J. Byrne and P. M. Reynolds, Aust. N.Z. J. Med., 1982,12, pp. 263–266. Fifty-three patients with advanced metastatic malignant melanoma were treated with DTIC, vincristine and cyclophosphamide in a 28 day cycle. In addition, 39 were vaccinated with BCG. The BCG treated group showed no significant advantage in response or survival over those treated with chemotherapy alone. Response rate in nodes draining vaccinated areas was not greater than that in equivalent nodes in non-BCG treated patients. Of 50 patients evaluable for response, two showed CR, 15 PR for an overall response rate of 34% (median duration 20 weeks, range 4–77 + weeks). Metastatic sites did not influence response rate. Median survival of all treated patients was 26 weeks, responders 42 weeks, non-responders 18 weeks, plt;0025. This regimen may be superior to DTIC alone.

Between January 1973 and January 1979, 131 patients with malignant non-Hodgkin's lymphomas (107 lymphocytic lymphomas, 24 histiocytic lymphomas) were treated with cyclophosphamide-vincristin-prednisone (CVP) either alone or combined with Adriamycin (CVP-A). Stage I and II lymphocytic lymphomas were all treated by CVP combined with radiotherapy. The survival curve for this group of patients plateaued at 89% from the 12th to the 60th month, which was the endpoint of the study. For Stage III and IV nodular lymphocytic lymphomas, actuarial survival was 69% at five years in the CVP-treated group as compared to 54% at three years in the group treated with CVP-A. For Stage III and IV diffuse lymphocytic lymphomas, the complete response rate and median survival were respectively 25% and 24 months in patients treated with CVP, as compared to 67% (P less than 0.01) and 26 months in the group treated with CVP-A. For histiocytic lymphomas, the complete response rate was 50% in the CVP-treated group as compared to 83% in the group treated with CVP-A. Most remarkable was the fact that while in the CVP treated group median survival was only 17 months, the small group of patients treated with CVP-A exhibited considerably improved survival with a horizontal survival curve at 90% after 36 months (12 patients). These results show that the CVP protocol remains an excellent treatment for nodular lymphocytic lymphomas. The addition of Adriamycin (CVP-A) as well as its inclusion in other drugs combination, has raised hopes for remissions of long duration and even for cures in patients with histiocytic lymphomas. Finally, in diffuse lymphocytic lymphomas, efforts will have to be pursued to improve the prognosis which remains poor despite the increased complete response rate achieved by the addition of Adriamycin.

From 1976 to 1981, 26 patients with sarcomas of the female genital tract were treated with combination chemotherapy consisting of cyclophosphamide, vincristine, adriamycin, and dimethyl-triazeno imidazole carboxamide (CYVADIC). Twenty-three percent achieved an objective response including complete response in 11.5%. The 23% response rate was achieved in patients who had extensive prior treatment with other chemotherapeutic regimens and/or radiation therapy. Therefore, the use of CYVADIC as first-line chemotherapy for sarcomas of the female genital tract not amenable to surgery or radiation therapy may result in significantly higher response rates than the 23% in the present series.

Zwischen Dezember 1973 und November 1978 wurden 31 Osteo-sarkompatienten mit einer Kombination aus Cyclophosphamid, Vincristin, Adriamycin und DTIC (CYVADIC) behandelt. 11 von 19 Patienten mit lokalis

小細胞性未分化癌30例に対してCOM療法を行った. Endoxan, Vincristine, Methotrexateを第1日, 第5日に点滴静注した. 2コース後に効果判定をした, 30例中23例に原発巣に関して放射線照射を行った. 結果はCOM単独では有効率70%(CR: 27%, PR: 43%) COM+Rでは有効率91%(CR: 56%, PR: 35%) を示した. 局所の再発についてみると照射群は23例中1例で再発まで8ヵ月であったのに対して, 非照射群は7例中4例認め再発まで1～3ヵ月であった. また全症例の50%生存期間は8ヵ月であった. COMの副作用には重篤なものはなく白血球数4000/mm3以下を示したものは9例認めたがいずれも一過性ですみやかに改善されたCOM+Rは有効率の改善に有力でありひいては生存期間の延長をもたらすものと考える.

Thirty-nine patients with small cell lung cancer were treated with large dose intravenous cyclophosphamide combined with vincristine. Sequential split-course radiotherapy was added when the gross disease was limited to one hemithorax and draining scalene nodes. Fifteen of 16 patients in the limited disease category showed objective response, eight of which were complete. Fourteen of 23 patients in the extensive disease category yielded an objective response, six of which were complete. The median survival for complete responders was 48 weeks, 38 weeks for partial responders and 14 weeks for non-responders. The difference between responders and non-responders was statistically significant. The major toxicity was myelosuppression with a median leukocyte nadir of 500/mm-3 noted on treatment day no. 15. Prompt recovery was the rule. Toxicity appeared to be cumulative for patients receiving radiotherapy. These results are superior to those evolving from treatment with cyclophosphamide as a solitary agent.

The M-2 protocol was administered every 5 weeks to 25 patients with stage III and IV chronic lymphocytic leukemia (CLL). Complete remission (CR; absence of all clinical and bone marrow evidence of leukemia including normal immune markers for monoclonal disease) and partial remission (PR; greater than 50% decrease in organ enlargement and reduction of WBC count to below 15,000 X 10(6)/l) were achieved in 20 and 48%, respectively. A median number of 24 cycles of therapy was required to produce a CR. The median duration of unmaintained remission was 12 months. All CR patients are still surviving. The median survival of the PR patients and the overall groups is 21 months. To improve the CR rate and survival in patients with advanced CLL, more effective methods of determining residual leukemic cells and different treatment strategies will be needed.

Thirty-five patients with advanced lymphosarcoma (32 without previous therapy) were treated with intensive 5-day courses of cyclophosphamide and prednisone, with vincristine given on the f...