A pre-implementation examination of barriers and facilitators of an electronic prospective surveillance model for cancer rehabilitation: a qualitative study.

BACKGROUND: An electronic Prospective Surveillance Model (ePSM) uses patient-reported outcomes to monitor symptoms along the cancer pathway for timely identification and treatment. Randomized controlled trials show that ePSMs can effectively manage treatment-related adverse effects. However, an understanding of optimal approaches for implementing these systems into routine cancer care is limited. This study aimed to identify barriers and facilitators prior to the implementation of an ePSM to inform the selection of implementation strategies. METHODS: A qualitative study using virtual focus groups and individual interviews was conducted with cancer survivors, oncology healthcare providers, and clinic leadership across four cancer centres in Canada. The Consolidated Framework for Implementation Research (CFIR) guided the interviews and analysis of barriers and facilitators based on five domains (intervention characteristics, individual characteristics, inner setting, outer setting, and process). RESULTS: We conducted 13 focus groups and nine individual interviews with 13 patient participants and 56 clinic staff. Of the 39 CFIR constructs, 18 were identified as relevant determinants to the implementation. The adaptability, relative advantage, and complexity of an ePSM emerged as key intervention-level factors that could influence implementation. Knowledge of the system was important at the individual level. Within the inner setting, major determinants were the potential fit of an ePSM with clinical workflows (compatibility) and the resources that could be dedicated to the implementation effort (readiness for implementation). In the outer setting, meeting the needs of patients and the availability of rehabilitation supports were key determinants. Engaging various stakeholders was critical at the process level. CONCLUSIONS: Improving the implementation of ePSMs in routine cancer care has the potential to facilitate early identification and management of treatment-related adverse effects, thereby improving quality of life. This study provides insight into important factors that may influence the implementation of an ePSM, which can be used to select appropriate implementation strategies to address these factors.

TAZ upregulates MIR-224 to inhibit oxidative stress response in multiple myeloma.

BACKGROUND: Oxidative stress within the bone marrow niche of multiple myeloma contributes to disease progression and drug resistance. Recent studies have associated the Hippo pathway with miRNA biogenesis and oxidative stress in solid tumors. Oxidative stress and miRNA pathway inter-relates in several cancers. Our group recently showed that TAZ functions as a tumor suppressor in MM. However, the role of TAZ in oxidative stress in MM is unknown. AIMS: We sought to examine the role of TAZ in myeloma cells' response to BM oxidative stress. We postulated that TAZ might be associated with an oxidative stress phenotype and distinct miRNA signature in MM. METHODS AND RESULTS: Using human myeloma cell lines and clinical samples, we demonstrate that TAZ promotes myeloma cells' sensitivity to oxidative stress and anticancer-induced cytotoxicity by inducing miR-224 to repress the NRF2 antioxidant program in MM. We show that low expression of TAZ protein confers an oxidative stress-resistant phenotype in MM. Furthermore, we provide evidence that overexpression of miR-224 in myeloma cells expressing low amounts of TAZ protein inhibits cell growth and enhances sensitivity to anti-myeloma therapeutics. CONCLUSION: Our findings uncover a potential role for TAZ in oxidative stress response in MM via the miR-224-NRF2 molecular pathway. This provides the scientific ground to explore miR-224 as a potential molecular target to modify TAZ expression and enhance myeloma sensitivity to treatment.

MST1 downregulates TAZ tumor suppressor protein in multiple myeloma and is a potential therapeutic target.

We have previously reported that transcriptional activator with PDZ-binding motif (TAZ) functions as a tumor suppressor in multiple myeloma (MM). MST1 is a serine-threonine kinase upstream of the Hippo-signaling pathway that functions as a tumor suppressor in many non-hematologic malignancies. However, its role in hematologic malignancies, including MM is still poorly understood. In this article, we provide evidence that MST1 expression is higher in MM and negatively correlates with TAZ expression in both cell lines and patient samples. High MST1 expression was associated with poor clinical outcomes. Genetic or pharmacologic inhibition of MST1 leads to increased TAZ expression and cell death. Importantly, MST1 inhibitors sensitize myeloma cells to frontline antimyeloma agents-lenalidomide and dexamethasone. Taken together, our data reveal a key role for MST1 in MM pathogenesis and provide evidence to explore the therapeutic potential of using MST inhibitors to upregulate TAZ expression in MM to promote response to anticancer agents.

Implementation of electronic prospective surveillance models in cancer care: a scoping review.

BACKGROUND: Electronic prospective surveillance models (ePSMs) for cancer rehabilitation include routine monitoring of the development of treatment toxicities and impairments via electronic patient-reported outcomes. Implementing ePSMs to address the knowledge-to-practice gap between the high incidence of impairments and low uptake of rehabilitation services is a top priority in cancer care. METHODS: We conducted a scoping review to understand the state of the evidence concerning the implementation of ePSMs in oncology. Seven electronic databases were searched from inception to February 2021. All articles were screened and extracted by two independent reviewers. Data regarding the implementation strategies, outcomes, and determinants were extracted. The Expert Recommendations for Implementing Change taxonomy and the implementation outcomes taxonomy guided the synthesis of the implementation strategies and outcomes, respectively. The Consolidated Framework for Implementation Research guided the synthesis of determinants based on five domains (intervention characteristics, individual characteristics, inner setting, outer setting, and process). RESULTS: Of the 5122 records identified, 46 interventions met inclusion criteria. The common implementation strategies employed were "conduct educational meetings," "distribute educational materials," "change record systems," and "intervene with patients to enhance uptake and adherence." Feasibility and acceptability were the prominent outcomes used to assess implementation. The complexity, relative advantage, design quality, and packaging were major implementation determinants at the intervention level. Knowledge was key at the individual level. At the inner setting level, major determinants were the implementation climate and readiness for implementation. At the outer setting level, meeting the needs of patients was the primary determinant. Engaging various stakeholders was key at the process level. CONCLUSIONS: This review provides a comprehensive summary of what is known concerning the implementation of ePSMs. The results can inform future implementation and evaluation of ePSMs, including planning for key determinants, selecting implementation strategies, and considering outcomes alongside local contextual factors to guide the implementation process.

Nanoparticle surface-enhanced Raman spectroscopy as a noninvasive, label-free tool to monitor hematological malignancy.

Aim: Monitoring minimal residual disease remains a challenge to the effective medical management of hematological malignancies; yet surface-enhanced Raman spectroscopy (SERS) has emerged as a potential clinical tool to do so. Materials & methods: We developed a cell-free, label-free SERS approach using gold nanoparticles (nanoSERS) to classify hematological malignancies referenced against two control cohorts: healthy and noncancer cardiovascular disease. A predictive model was built using machine-learning algorithms to incorporate disease burden scores for patients under standard treatment upon. Results: Linear- and quadratic-discriminant analysis distinguished three cohorts with 69.8 and 71.4% accuracies, respectively. A predictive nanoSERS model correlated (MSE = 1.6) with established clinical parameters. Conclusion: This study offers a proof-of-concept for the noninvasive monitoring of disease progression, highlighting the potential to incorporate nanoSERS into translational medicine.

Cancer patient quality of life is achieved by reassurance from informed doctors using the best clinical tools. Confirming the earliest detection or absence of disease ensures treatment is timely and recovery optimal. Here we show the potential for a new tool to be developed to reassure patients and inform doctors. We examined the 'chemical fingerprints' (Raman spectroscopic profiling) of patient's blood, enhanced by gold nanoparticles with a double-referenced machine learning algorithm. Teaching a machine to learn as it works ensures it is improving how it finds clinically important features in the chemical fingerprint. This helps patients live more confidently with cancer or in cancer recovery. Eventually, once fully trained and translated into a real-world hospital application, this could improve patient outcomes and quality of life.

Weekly carfilzomib plus cyclophosphamide and dexamethasone in the treatment of relapsed/refractory multiple myeloma: Final results from the MCRN-003/MYX.1 single arm phase II trial.

The MCRN-003/CCTGMYX.1 is a single arm phase II trial of weekly carfilzomib, cyclophosphamide and dexamethasone (wKCd), exploring a convenient immunomodulator (IMiD)-free regimen in relapsed myeloma. Weekly carfilzomib (20/70 mg/m2 ), dexamethasone 40 mg and cyclophosphamide 300 mg/m2 was delivered over 28-day cycles. The primary endpoint was overall response after four cycles. Secondary endpoints included toxicity, response depth, PFS and OS. Exploratory endpoints included the impact of cytogenetics, prior therapy exposure and serum free light chain (sFLC) escape; 76 patients were accrued. The ORR was 85% (68% ≥very good partial response [VGPR] and 29% ≥complete response [CR]). The median OS and PFS were 27 and 17 months respectively. High-risk cytogenetics conferred a worse ORR (75% vs. 97%, p = .013) and median OS (18 months vs. NR, p = .002) with a trend toward a worse median PFS (14 vs. 22 months, p = .06). Prior proteasome inhibitor (PI) or lenalidomide did not influence OS or PFS. The sFLC was noted in 15% of patients with a median PFS of 17 months when included as a progression event. The most common ≥ grade 3 non-hematologic adverse events were infectious (40%), vascular (17%) and cardiac (15%). The wKCD is a safe and effective regimen in relapse, especially for patients ineligible for lenalidomide-based therapies.

Real-world outcomes with bortezomib-containing regimens and lenalidomide plus dexamethasone for the treatment of transplant-ineligible multiple myeloma: a multi-institutional report from the Canadian Myeloma Research Group database.

Bortezomib-containing regimens (BCRs) represented standard, first-line therapy for transplant-ineligible multiple myeloma (TIMM) in Canada until the introduction of lenalidomide and low-dose dexamethasone (Ld). However, little comparative data exist to inform the selection of regimens. We assessed the outcomes for TIMM patients treated with cyclophosphamide, bortezomib and dexamethasone or prednisone (CyBorD/P), bortezomib, melphalan and prednisone (VMP), bortezomib and dexamethasone or prednisone (VD/P) and lenalidomide and low-dose dexamethasone (Ld) using the Canadian Myeloma Research Group database. Of 1156 TIMM patients evaluated, 82% received bortezomib combinations while 18% received Ld. Median progression-free survival (PFS) was 21·0, 21·1, 13·2 and 28·5 months (P = 0·0002) and median overall survival (OS) was 52·0, 63·6, 30·8 and 65·7 months (P < 0·0001) in the CyBorD/P, VMP, VD/P and Ld groups respectively. There was no significant difference in PFS and OS between the two triplet bortezomib regimens (VMP and CyBorD/P). Ld was associated with a longer PFS but not a significantly superior OS to date. Outcomes with the bortezomib-steroid doublet were inferior (VD/P). However, multivariable analysis identified features related to disease biology as the most important prognostic factors for PFS and OS. Such factors, as well as those affecting the physician's choice of regimen, are likely to influence the results observed with different regimens. This study demonstrated real-world outcomes in TIMM similar to those reported in clinical trials.

Targeting NK Cell Inhibitory Receptors for Precision Multiple Myeloma Immunotherapy.

Innate immune surveillance of cancer involves multiple types of immune cells including the innate lymphoid cells (ILCs). Natural killer (NK) cells are considered the most active ILC subset for tumor elimination because of their ability to target infected and malignant cells without prior sensitization. NK cells are equipped with an array of activating and inhibitory receptors (IRs); hence NK cell activity is controlled by balanced signals between the activating and IRs. Multiple myeloma (MM) is a hematological malignancy that is known for its altered immune landscape. Despite improvements in therapeutic options for MM, this disease remains incurable. An emerging trend to improve clinical outcomes in MM involves harnessing the inherent ability of NK cells to kill malignant cells by recruiting NK cells and enhancing their cytotoxicity toward the malignant MM cells. Following the clinical success of blocking T cell IRs in multiple cancers, targeting NK cell IRs is drawing increasing attention. Relevant NK cell IRs that are attractive candidates for checkpoint blockades include KIRs, NKG2A, LAG-3, TIGIT, PD-1, and TIM-3 receptors. Investigating these NK cell IRs as pathogenic agents and therapeutic targets could lead to promising applications in MM therapy. This review describes the critical role of enhancing NK cell activity in MM and discusses the potential of blocking NK cell IRs as a future MM therapy.

Antimyeloma Potential of Caffeic Acid Phenethyl Ester and Its Analogues through Sp1 Mediated Downregulation of IKZF1-IRF4-MYC Axis.

Caffeic acid phenethyl ester (CAPE, 2), a natural compound from propolis, is a well-documented antitumor agent with nuclear factor kappa B (NF-κB) inhibitory activity. Key transcription factors regulated by NF-κB, namely, interferon regulatory factor-4 (IRF4) and octameric binding protein-2 (OCT2), are implicated in the tumorigenesis of multiple myeloma (MM), an incurable bone marrow cancer. Adverse effects and resistance to current chemotherapeutics pose a great challenge for MM treatment. Hence, the structure-activity relationships of CAPE (2) and 21 of its analogues were evaluated for their antimyeloma potential. Preclinical evaluation revealed that CAPE (2) and the 3-phenylpropyl (4), 2,5-dihydroxycinnamic acid 3-phenylpropyl ester (17), and 3,4-dihydroxycinnamic ether (22) analogues inhibited human myeloma cell growth. Analogue 4 surpassed CAPE (2) and lenalidomide in showing strong apoptotic effects with a remarkable decrease in IRF4 levels. The analogue 17 exhibited the most potent anti-MM activity. The downregulation of specificity protein 1 (Sp1) and the IKZF1-IRF4-MYC axis by CAPE (2) analogues 4 and 17 revealed their novel mechanism of action. The analogues showed no adverse cytotoxic effects on normal human cells and exhibited appropriate in silico pharmacokinetic properties and drug-likeness. These findings suggest the promising application of CAPE (2) analogues to target Ikaros (IKZF1)/IRF4 addiction, the so-called Achilles heel of myeloma, for better treatment outcomes.

Immunohistochemical validation study of 15-gene biomarker panel predictive of benefit from adjuvant chemotherapy in resected non-small-cell lung cancer: analysis of JBR.10.

OBJECTIVE: There are no validated approaches to predict benefit from adjuvant chemotherapy for resected patients with non-small-cell lung cancer (NSCLC). The aim of this study was to translate a 15-gene mRNA expression profile published by Zhu et al, shown to be prognostic and predictive of benefit, into a readily applicable immunohistochemistry (IHC) panel. METHODS: For seven of the genes in the gene expression profile (GEP) for which suitable commercial antibodies were available, we semiquantitatively assessed the IHC expression and prognostic significance for 173 patients treated at the Saint John Regional Hospital (SJRH). Cut-offs for high and low expression were defined for each marker and applied to IHC scores from 291 of the 482 patients in JBR.10, including patients on both the adjuvant chemotherapy and observation arms. The prognostic and predictive value of these markers on overall survival (OS) or recurrence-free survival (RFS) was assessed by Cox regression models. RESULTS: In the SJRH cohort, in 62 patients with resected stage II-III NSCLC, the prognostic significance of IHC assays for four proteins were concordant with Zhu's GEP results. Low FOSL2 (OS, HR=0.15; p=0.0001; RFS, HR=0.14; p<0.0001) and high STMN2 (RFS, HR=2.501; p=0.0197) were adverse prognostic factors. Low ATP1B1 and low TRIM14 expression trended toward worse OS and RFS. Validation of these markers with JBR.10 patients failed to show prognostic significance either individually or in combined risk classifications. Additionally, the interaction between these markers and chemotherapy treatment in predicting OS (FOSL2, p=0.52; STMN2 p=0.14; ATP1B1, p=0.33; TRIM14, p=0.81) or RFS (FOSL2, p=0.63; STMN2, p=0.12; ATP1B1, p=0.66; TRIM14, p=0.57) did not reach significance, individually or in combination panels. CONCLUSIONS: Zhu's GEP could not be translated into an IHC panel predictive of benefit from adjuvant chemotherapy. Future predictive biomarker analysis in the adjuvant NSCLC setting may need to focus on novel therapies.

TAZ functions as a tumor suppressor in multiple myeloma by downregulating MYC.

Multiple myeloma (MM) is an incurable blood cancer that is often characterized by amplification and overexpression of the MYC oncogene. Despite efforts, direct targeting of MYC is not yet possible; therefore, alternative strategies to inhibit MYC activity are necessary. TAZ is a transcriptional coactivator downstream of the Hippo-signaling pathway that functions as an oncogene in many solid tumors. However, its role in hematological malignancies is largely unexplored. Here, we show that, in contrast to solid tumors, expression of TAZ is lower in hematological malignancies, and that high expression of TAZ correlates with better patient outcomes. We further show that TAZ is hypermethylated in MM patient samples and in a panel of MM cell lines. Genetic overexpression of TAZ or pharmacological upregulation of TAZ by treatment with the demethylating agent decitabine induces apoptosis. Importantly, TAZ-induced apoptosis is independent of canonical Hippo components LATS1 or the TEA-domain family of transcription factors. Instead, RNA-sequencing analysis revealed that overexpression of TAZ represses a MYC transcriptional program and we show that increased TAZ expression correlates with decreased MYC expression in both cell-line models and patient samples. Furthermore, promoter derepression of TAZ expression sensitizes MM cell lines through a reciprocal reduction in MYC expression using additional therapeutics such as bortezomib, trichostatin A, and panobinostat. Our findings uncover an unexpected role for TAZ in MM tumorigenesis and provide a compelling rationale for exploring the therapeutic potential of upregulating TAZ expression to restore sensitivity to specific therapeutics in MM.

A phase I study of romidepsin, gemcitabine, dexamethasone and cisplatin combination therapy in the treatment of peripheral T-cell and diffuse large B-cell lymphoma; the Canadian cancer trials group LY.15 study†.

We investigated GDP (gemcitabine, 1000 mg/m2 IV d1, d8; dexamethasone, 40 mg po d1-4; cisplatin, 75 mg/m2 IV d1) combined with romidepsin on days 1 and 8 every 21 days to a maximum of six cycles in a standard 3 + 3, phase I dose escalation trial for patients with relapsed/refractory peripheral T-cell (PTCL) or diffuse large B-cell (DLBCL) lymphoma (NCT01846390). After treating four patients, gemcitabine and romidepsin were given on days 1 and 15 every 28 days. On the 21-day schedule at 6 mg/m2 romidepsin, there were three dose-limiting toxicities (DLTs) among four patients. On the 28-day schedule, there were no DLTs at the 6, 8, or 10 mg/m2 dose. At 12 mg/m2, there were four observed grade 3 DLTs among six evaluable patients. Full doses of GDP can be combined with a recommended phase II romidepsin dose of 10 mg/m2 if given on a day 1, 15 every 28 days schedule.

Factors influencing middle managers' commitment to the implementation of innovations in cancer care.

OBJECTIVE: To identify and illuminate influences on middle managers' commitment to innovation implementation. METHODS: A qualitative study was conducted, employing the methods of grounded theory. Semi-structured interviews were used to collect data from middle managers (n = 15) in Nova Scotia and New Brunswick, Canada. Data were collected and analysed concurrently, using an inductive constant comparative approach. Data collection and analysis continued until theoretical saturation was reached. RESULTS: The data revealed middle managers contemplate two central issues in terms of their commitment to implementation, that is whether or not they fully engage in and support the implementation of a particular innovation. These issues are (1) ease of implementation and (2) potential benefit for patients. Middle managers' views and expectations related to ease of implementation are influenced by available resources, fit with setting, and stakeholder buy-in. Their views on patient benefit are influenced by external evidence of benefit and local gaps in care. CONCLUSIONS: These findings provide further insight into the factors that influence middle managers' commitment to innovation implementation, and how middle managers consider these factors in the context of their work settings.

Making It Happen: Middle Managers' Roles in Innovation Implementation in Health Care.

BACKGROUND: Middle managers are given scant attention in the implementation literature in health care, where the focus is on senior leaders and frontline clinicians. AIMS: To empirically examine the role of middle managers relevant to innovation implementation and how middle managers experience the implementation process. METHODS: A qualitative study was conducted using the methods of grounded theory. Data were collected through semistructured interviews with middle managers (N = 15) in Nova Scotia and New Brunswick, Canada. Participants were purposively sampled, based on their involvement in implementation initiatives and to obtain variation in manager characteristics. Data were collected and analyzed concurrently, using an inductive constant comparative approach. Data collection and analysis continued until theoretical saturation was reached. RESULTS: Middle managers see themselves as being responsible for making implementation happen in their programs and services. As a result, they carry out five roles related to implementation: planner, coordinator, facilitator, motivator, and evaluator. However, the data also revealed two determinants of middle managers' role in implementation, which they must negotiate to fulfill their specific implementation roles and activities: (1) They perform many other roles and responsibilities within their organizations, both clinical and managerial in nature, and (2) they have limited decision-making power with respect to implementation and must work within the parameters set by upper levels of the organization. LINKING EVIDENCE TO ACTION: Middle managers play an important role in translating adoption decisions into on-the-ground implementation. Optimizing their capacity to fulfill this role may be key to improving innovation implementation in healthcare organizations.

Salvage chemotherapy and autologous stem cell transplantation for peripheral T-cell lymphoma: a subset analysis of the Canadian Cancer Trials Group LY.12 randomized phase 3 study.

Peripheral T-cell lymphoma (PTCL) is a rare, heterogeneous malignancy. Of the 619 patients with relapsed and refractory (R/R) aggressive lymphoma enrolled in the Canadian Cancer Trials Group LY.12 phase 3 trial, 59 (9.5%) had PTCL. Among these, 81% had advanced stage disease, 41% had an International Prognostic Score ≥3, and 41% were refractory to primary therapy. Within the PTCL cohort, the overall response rate after two cycles of salvage chemotherapy was 36%; no difference was observed between dexamethasone, cytarabine, cisplatin (10/30, 33%), and gemcitabine, cisplatin, dexamethasone (11/29, 38%) therapy. At one year, event-free survival (EFS) was 16% and overall survival (OS) was 28%. For PTCL patients, who received autologous stem cell transplant, two-year EFS and OS were 21% and 42%, respectively. Patients with PTCL had inferior OS (HR 0.49, p < .0001) and EFS (HR 0.53, p < .0001) compared to B-cell lymphoma. Outcomes for patients with R/R PTCL are poor with currently available therapies.

A simple prognostic model for overall survival in metastatic renal cell carcinoma.

INTRODUCTION: The primary purpose of this study was to develop a simpler prognostic model to predict overall survival for patients treated for metastatic renal cell carcinoma (mRCC) by examining variables shown in the literature to be associated with survival. METHODS: We conducted a retrospective analysis of patients treated for mRCC at two Canadian centres. All patients who started first-line treatment were included in the analysis. A multivariate Cox proportional hazards regression model was constructed using a stepwise procedure. Patients were assigned to risk groups depending on how many of the three risk factors from the final multivariate model they had. RESULTS: There were three risk factors in the final multivariate model: hemoglobin, prior nephrectomy, and time from diagnosis to treatment. Patients in the high-risk group (two or three risk factors) had a median survival of 5.9 months, while those in the intermediate-risk group (one risk factor) had a median survival of 16.2 months, and those in the low-risk group (no risk factors) had a median survival of 50.6 months. CONCLUSIONS: In multivariate analysis, shorter survival times were associated with hemoglobin below the lower limit of normal, absence of prior nephrectomy, and initiation of treatment within one year of diagnosis.

Final report of a phase 2 clinical trial of lenalidomide monotherapy for patients with T-cell lymphoma.

BACKGROUND: Patients with T-cell lymphomas face a poorer prognosis compared with patients with B-cell lymphomas. New therapeutic approaches need to be developed to improve outcomes for these patients. METHODS: Forty patients with recurrent and refractory T-cell lymphomas other than mycosis fungoides and patients with untreated T-cell lymphoma who were not candidates for combination chemotherapy were prescribed oral lenalidomide at a dose of 25 mg daily on days 1 to 21 of each 28-day cycle, with standardized dose reductions for toxicity. The primary endpoint was overall response rate (ORR), and secondary endpoints were complete and partial response rates, progression-free survival (PFS), overall survival (OS), and safety. The authors also determined duration of response (DoR). RESULTS: A total of 40 patients were enrolled in the current study; 1 patient was subsequently deemed ineligible. The ORR was 10 of 39 patients (26%); 3 patients (8%) achieved complete responses and 7 patients achieved partial responses. Three patients had stable disease for ≥5 cycles. The median OS was 12 months (range <1 month to ≥69 months), the median PFS was 4 months (range, <1 month to ≥50 months), and the median DoR was 13 months (range 2 months to ≥37 months), including 5 responses that lasted >1 year. Toxicity was in keeping with the known safety profile of lenalidomide. Among the patients who had recurrent/refractory peripheral T-cell lymphoma (29 patients), the ORR was 24%, the median OS was 12 months, the median PFS was 4 months, and the median DoR was 5 months (range, 2 months to ≥37 months). CONCLUSIONS: In the current study, the use of oral lenalidomide monotherapy demonstrated clinically relevant efficacy among patients with systemic T-cell lymphomas. It appears to have excellent potential as an agent in combination therapy for patients with T-cell lymphoma.