Gene therapy represents ‘new paradigm’ for treatment of hematologic disorders

Researchers in hematology have long believed that gene therapy may provide a pathway to more effectively treat chronic genetic hematologic disorders, with the potential for functional cures in certain cases.

These diseases — such as beta-thalassemia major, Wiskott-Aldrich syndrome and X-linked severe combined immunodeficiency (SCID-X1) — arise due to mutations in genes that control the production of beta globin and other proteins that are essential for the production of healthy blood cells and normal immune system functioning.

These conditions affect thousands of children and adults around the world. Most need continual treatment, and they often are dependent on blood transfusions or require hematopoietic stem cell transplantation (HSCT), which can affect overall quality of life.

Early studies of gene therapy were hindered by the development of leukemias or myelodysplasia in certain patients.

However, results of several studies presented at the ASH Annual Meeting and Exposition in December suggest researchers have overcome those challenges, and that gene therapy soon could replace chronic treatment for these disorders.

“It has taken 30 years to work out all the details to make gene therapy effective in humans,” George Q. Daley, MD, PhD, professor of biological chemistry and molecular pharmacology at Harvard Medical School, as well as director of the Stem Cell Transplantation program at Dana-Farber/Boston Children’s Cancer and Blood Disorders Center, told HemOnc Today. “There has been slow and steady progress in the production of viral vectors that can efficiently infect blood stem cells, which required optimizing the manufacture of viruses so that they could achieve a high transduction efficiency for the transfer of genes. We heard [at ASH] that there are now several different types of vectors that are not only achieving a high level of efficiency in gene transfer, but are also avoiding the mishaps of genotoxicity.”

Research at ASH also showed the promise of gene therapy to treat hematologic malignancies via chimeric antigen receptor (CAR) T cells that are engineered to recognize specific targets and activate the immune system against the cancer.

“This targeted therapy is transformational,” Daley said. “It is a new paradigm in cancer care.”

HemOnc Today spoke with hematologists and researchers about the success of gene therapy studies so far, the potential limitations of this treatment approach, and the possible application of gene therapy for the treatment of severe hematologic malignancies.

Beyond HSCT

Results from the phase 1/2 NORTHSTAR study presented at ASH demonstrated the promising efficacy of gene therapy for patients with beta-thalassemia major, a hereditary disease that causes a defect in production of hemoglobin required for red blood cells.

Approximately 60,000 infants are born each year with the condition, caused by a mutation in the HBB gene. The disorder can lead to severe anemia and can be fatal if untreated.

Although allogeneic HSCT often is curative, the risks associated with the procedure limit its use to patients with unaffected, matched-sibling donors, available in fewer than 25% of cases.

“These individuals are generally diagnosed in the first year of life and need to start red blood cell transfusions for this disorder,” Mark C. Walters, MD, a researcher on the NORTHSTAR study and program director for blood and marrow transplantation and the cord blood program at University of California, San Francisco’s Benioff Children’s Hospital, said during a press conference at ASH. “These transfusions are lifelong and administered monthly, but they contain more iron than can be eliminated naturally, so patients must also receive a medicine to leech excess iron from the body.”

Researchers created a drug product, LentiGlobin BB305 (Bluebird Bio), which uses a non-communicable virus to deliver a fully functioning HBB gene to the patient’s blood-producing stem cells. The goal is for the modified stem cells to produce enough hemoglobin to reduce, or even eliminate, the need for blood transfusions.

Walters presented data from 13 patients (median age, 21 years; range, 16-35) with transfusion-dependent beta-thalassemia major. Prior to going on study, these patients received a median of 170 mL/kg (range, 137-233) of transfused red blood cells per year.

Researchers collected patients’ stem cells and transduced them with LentiGlobin BB305 lentiviral vector to create the drug product. Prior to infusion, the patients underwent myeloablation with busulfan.

Five of nine patients monitored for at least 6 months after infusion achieved transfusion independence, and at data cut-off, three had remained transfusion independent for more than 1 year.

All five patients who achieved transfusion independence have HBB gene mutations that appear to produce some level of functional hemoglobin. The other four patients — all of whom have beta 0 (0/0) disease and, thus, may require a higher level of corrected hemoglobin — reduced their transfusion requirement by at least 50%.

“All patients enrolled in the trial experienced a clinical benefit and, in some cases, their transfusions have stopped,” Walters said during his presentation. “This appears to be a safe treatment, in that all patients recovered completely after infusion. To date, these analyses show no evidence of activation of the cancer-causing gene in the stem cells infused.”

The safety profile also appears promising.

“Compared with a bone marrow transplant, which is the only curative treatment that has been proved, this appears to be safer,” Walters said. “None of these patients have had a life-threatening complication. Because the treatment uses the patients’ own stem cells, this bypasses the need to find a healthy bone marrow donor. Thus, it should be more broadly available to patients with this disease.”

However, barriers remain, according to Daley, who moderated ASH’s gene therapy press conference.

“The degree of protein expression that can be achieved [through gene therapy] remains a limitation,” Daley said in an interview. “Further research and advances are needed. However, patients who produce some of their own hemoglobin went from transfusion dependence to transfusion independence, and that is remarkable.”

Overall, these findings could represent a major shift in the treatment of beta-thalassemia major, Daley added.

“For a significant number of the kids being treated — and, in many cases now, the adults — there can be a major improvement in quality of life,” Daley said. “In the long run, some of these patients will have been cured of their disease.”

’A valuable option’

Wiskott-Aldrich syndrome — caused by a mutation in the WAS gene — occurs in one to 10 males per million births worldwide, according to data from the NIH’s Genetic Home Reference. The condition is even less common among females because of its X-linked pattern of inheritance.

Patients with the disorder have immune deficiency and a reduced ability to form blood clots, leading to risk for easy bruising and prolonged bleeding episodes.

HSCT can be curative for patients with this disease; however, its risks — coupled with the frequent lack of a matched-sibling donor — limit its use in this population.

“This is an area where the accepted therapy has some complications and some limitations,” David A. Williams, MD, president of Dana-Farber/Boston Children’s Cancer and Blood Disorders Center and Leland Fikes Professor of Pediatrics at Harvard Medical School and immediate past president of ASH, told HemOnc Today. “In this case, there are barriers to successful transplantation. Use of gene therapy to correct autologous cells eliminates the need to identify a suitable donor. Potential complications associated with transplant modalities — such as graft-versus-host disease [GVHD] — can also be eliminated through gene therapy.”

Further, older patients who undergo HSCT tend to experience poorer outcomes, according to Francesca Ferrua, MD, a hematologist at San Raffaele Telethon Institute for Gene Therapy in Milan.

“Without an available donor for transplant, patients with Wiskott-Aldrich syndrome do not have any curative options,” Ferrua told HemOnc Today. “You can give them supportive treatment, but they will have a very poor quality of life. Without any curative intervention, classic Wiskott-Aldrich syndrome results in premature death, often during childhood.”

Consequently, researchers have recognized Wiskott-Aldrich syndrome as a prime candidate for innovative interventional treatments.

Ferrua and colleagues used a lentiviral vector to correct the expression of the WAS gene in eight patients (median age, 2.2 years; range, 1.1-12.4) with Wiskott-Aldrich syndrome in order to reduce their risk for infections and bleeding complications.

Results of the phase 1/2 study — presented at ASH — indicated all patients remained alive after a median follow-up of 3.4 years (range, 0.2-5.5).

Six patients followed for longer than 2 years experienced a dramatic reduction in severe infections and bleeding episodes. These patients also had mean platelet counts that progressively increased, from 13.4 ± 7.8 x 10⁹/L prior to therapy to 57 ± 18.7 x 10⁹/L up to 42 months after treatment. All patients ceased platelet transfusion following gene therapy, with a median time to independence of 3 months (range, 0.5-8.7).

Patients with more than 1-year follow-up (n = 7) discontinued anti-infection prophylaxis and no longer required a protective environment. Five patients ceased immunoglobulin supplementation.

Further, researchers did not observe adverse reactions after the infusion, and the reduced-intensity conditioning appeared well tolerated.

“The results of this trial confirm the potential for the benefit of using gene therapy approaches of autologous hematopoietic stem cells and vectors in correcting genetic defects,” Alessandra Biffi, MD, director of gene therapy at Dana-Farber/Boston Children’s Cancer and Blood Disorders Center, told HemOnc Today. “This is a valuable therapeutic option for these patients, and is probably the first step for further improvement in these kinds of hematologic diseases.”

Photo by Sam Ogden for Dana-Farber/Boston Children’s Cancer and Blood Disorders Center.

Although gene therapy for Wiskott-Aldrich syndrome led to the development of leukemia in previous studies, this effect has not been observed in any patient treated on this trial.

“The vectors have been improved with respect to safety, following setbacks in trials conducted in the early 2000s, where leukemia was developed by patients in multiple trials,” Williams said. “Those led to a new series of vector designs that have maintained efficacy and attenuated safety issues, which have allowed a broader application of the technology from a disease standpoint.”

However, it remains to be seen whether gene therapy also can have a good effect on platelet count in addition to the immune system, Williams added.

“The effects on the immune system appear to suggest uniform improvement, and ongoing studies will address any remaining problems with the platelet system,” he said.

Overall, these results may support studies in additional indications, Ferrua said.

“Our findings will influence future research by giving evidence that lentiviral gene therapy is not only effective but corrective in patients with inherited diseases,” she said. “Every disease is different, so we will have to perform lots of studies, but there may be benefit found for the treatment of other inherited genetic conditions.”

Expanded applications

SCID-X1 — often referred to as bubble boy disease — affects approximately one of every 100,000 babies born in the United States, according to estimates from the Genetic Science Learning Center at University of Utah Health Sciences.

As with other hematologic disorders, HSCT presents a curative option for patients with SCID-X1. Patients lacking a matched-sibling donor can be treated with haploidentical parental HSCT; however, this treatment often only restores T-cell immunity.

Patients who are not candidates for matched-sibling HSCT require lifelong immunoglobulin treatment. They also are at risk for chronic infections, warts, malnutrition, and progressive lung and gut conditions, according to Suk See De Ravin, MD, PhD, staff clinician at the NIH’s Laboratory of Host Defenses.

“These patients are alive, but many suffer the long-term consequences of the partial immune reconstitution and continue to face problems,” De Ravin said during the ASH press conference. “Gene therapy, as an alternative treatment to transplant, can effectively rebuild the immune system.”

De Ravin presented data from a study that evaluated lentiviral hematopoietic stem cell gene therapy as a salvage treatment for patients with incomplete correction after allogeneic haploidentical HSCT. The analysis included data from five patients aged older than 2 years (aged 7, 10, 16, 23 and 24 years) who had worsening immune dysfunction and were dependent on immunoglobulin supplementation despite prior haploidentical HSCT.

Because SCID-X1 is caused by mutations in the IL2RG gene, researchers used a lentiviral vector to insert a normal form of IL2RG into patients’ stem cells. Patients also underwent low-dose marrow conditioning prior to the infusion with 6 mg/kg IV busulfan to enhance engraftment.

At the time of the ASH presentation, patient follow-up ranged from 3 months to 3 years.

The two oldest patients — who had the longest follow-up — experienced stable engraftment of gamma chain-expressing cells, with an increasing proportion of immune cells with corrected genes, specifically for T cells (13% to 55%; 0.13-0.55 vector genome [vg]/cell), B cells (38%; 0.38 vg/cell) and natural killer (NK) cells (56% to 76%; 0.56-0.76 vg/cell).

The increase in NK cells in the 24-year-old patient corresponded with an improvement in previously chronic warts. Both older patients produced immunoglobulin and antigen-specific responses with protective titer response to immunization, as well as clearance of chronic norovirus and resolution of protein-losing enteropathy.

Further, the early gene marking trend among the three most recently treated patients appeared comparable, if not better, than patients treated earlier, De Ravin said.

Williams — whose primary area of research includes the treatment of SCID-X1 with gene therapy — noted that the trial outcomes may have had more to do with the use of chemotherapy than viral vector used in the gene therapy approach.

“Although this trial represents a very small number of patients, the novel approach taken by the research group to include chemotherapy conditioning prior to giving back the gene-modified cells seems to have been key to the success of the procedure,” Williams said. “In my view, it has less to do with the vector and more to do with the conditioning.”

Further, the therapy did not appear to reverse organ damage.

“Despite an improvement in immune function, one patient unfortunately died of a right lung bronchiectatic bleed after 2 and a quarter years post-gene therapy,” De Ravin said. “This tells us that gene therapy cannot correct preexisting lung damage. This supports a need for early intervention to improve immunity before such damage occurs.”

Despite these concerns, the outcomes demonstrate a benefit to a population with an unmet medical need.

“The patients in this trial were older and had previously undergone a bone marrow transplant,” Williams said. “Gene therapy was offered as a rescue procedure here. The data looked quite good, and [the results] expand the applications of gene therapy.”

Potential in blood cancers

A considerable amount of early gene therapy research has centered on the treatment of chronic benign hematologic disorders. However, experts believe gene therapy also could benefit patients with hematologic malignancies.

“The potential for gene therapy in blood cancers is clear,” Biffi said. “The clinical evidence is that approaches similar to the ones mentioned for benign diseases such as thalassemia or SCID-X1 could work in the cancer setting. However, the use of gene therapy for cancer is mostly focused on the use of mature cells, as opposed to hematopoietic stem cells for benign disorders.”

The basics of the gene therapy approach differ when used to treat malignant conditions.

“When you use the strategy of gene transfer to target cancer, it falls under the general rubric of gene therapy,” Daley said. “Gene modification is used to engineer a patient’s own T cells to seek out and destroy their cancer, which is distinct from trying to complement a gene deficiency resulting from an inborn error.

Two studies presented at ASH by James N. Kochenderfer, MD, investigator in the experimental transplantation and immunology branch of the NCI’s Center for Cancer Research, showed the potential for gene therapy to treat hematologic malignancies via T Cells carrying genes that encode CARs.

In one of the studies, researchers engineered T cells with CARs directed against CD19 for use in patients with B-cell malignancies who experienced disease progression after HSCT. CD19 is expressed on the surface of most B cells, and the CAR T cells are designed to attack the B cell after recognizing CD19.

“New treatments are needed for patients with progressive B-cell malignancies after allogeneic HSCT,” Kochenderfer told HemOnc Today. “Progressive malignancy is one of the leading causes of death among these patients, and one of the main treatments for progressive malignancy after transplant — the infusion of unmanipulated allogeneic donor lymphocytes — is very inconsistently effective and often causes GVHD.”

Among 20 patients who received a single infusion of CAR T cells derived from their HSCT donor — and transfused without any conditioning regimens — nine achieved remission (complete remission, n = 6; partial remission, n = 3). The most durable remission, in a patient with chronic lymphocytic leukemia, has been sustained for over 36 months, Kochenderfer said.

No patients experienced new-onset GVHD, and other adverse events were mild and transient.

“Without chemotherapy or other treatments, allogeneic anti-CD19 T cells can cause remission of malignancies that were progressive, despite allogeneic transplantation, chemotherapy or other treatments,” Kochenderfer said. “The CAR cells did not cause GVHD. We are going to try to improve how the CAR T cells are manufactured in an attempt to improve efficacy.”

Kochenderfer also presented results from a first in-humans study of CAR T cells in patients with multiple myeloma. These CAR T cells were engineered to target B-cell maturation antigen (BCMA), a protein expressed by normal and malignant plasma cells. BCMA is under investigation as a target for multiple myeloma — a disease of plasma cells — because it is only expressed by plasma cells and a few B cells.

The analysis included data from 12 patients with heavily pretreated, advanced disease (median prior therapy lines, n = 7).

Patients received a chemotherapy regimen of cyclophosphamide (300 mg/m²) and fludarabine (30 mg/m²) for 3 days, followed by a single infusion of CAR-modified T cells at one of four dose levels (0.3 x 10⁶, 1 x 10⁶, 3 x 10⁶ or 9 x 10⁶ CAR-positive T cells/kg of body weight).

Six patients received the two lowest doses. The researchers reported a transient partial remission in one patient, lasting 2 weeks. The other five patients achieved stable disease.

Of the three patients assigned to the third dose level, two achieved stable disease. The other patient obtained a very good partial remission, with complete elimination of myeloma bone disease confirmed by PET scan, normalization of serum free light chains and clearance of bone marrow plasma cells.

The greatest responses were seen in the two patients who received the highest dose. One of these patients — who had multiple myeloma that comprised greater than 90% of total bone marrow cells prior to treatment — achieved a stringent complete remission 2 months following the CAR-BCMA T-cell infusion.

The other patient — who had 80% bone marrow plasma cells prior to treatment — had undetectable myeloma in the bone marrow plasma cells 4 weeks after infusion, but had not yet achieved complete remission.

“Multiple myeloma was completely eliminated from the bone marrow of these two patients,” Kochenderfer said. “The elimination of disease from the first patient was particularly impressive given how advanced the status of his disease was.”

A multicenter clinical trial of CAR T cells for multiple myeloma is planned for early this year, Kochenderfer said.

“The CAR T-cell approach already shows great potential for future cancer care,” Biffi said. “Gene therapy has gone through many steps of improvement over the years, and this is one area of significant improvement.”

Moreover, studies presented at ASH may have demonstrated how researchers have unlocked the potential of gene therapy for benign and malignant conditions alike.

“We started working on gene therapy in the early 1980s, and what we are seeing is the natural progression that takes place in any innovative field,” Williams said. “We are seeing a series of steps leading to new approaches, which tend to be informed by the problems in early research. As such, the successes begin to accelerate as time goes on.” – by Cameron Kelsall

References:

The following abstracts were presented at the ASH Annual Meeting and Exposition; Dec. 5-8, 2015; Orlando, Fla.

Ali SA, et al. Abstract LBA-1.

Brudno JN, et al. Abstract 99.

De Ravin SS, et al. Abstract 261.

Ferrua F, et al. Abstract 259.

Walters MC, et al. Abstract 201.

For more information:

Alessandra Biffi, MD, can be reached at alessandra.biffi@childrens.harvard.edu.

George Q. Daley, MD, PhD, can be reached at george.daley@childrens.harvard.edu.

Francesca Ferrua, MD, can be reached at ferrua.francesca@hsr.it.

James N. Kochenderfer, MD, can be reached at kochendj@mail.nih.gov.

David A. Williams, MD, can be reached at david.williams@childrens.harvard.edu.

Disclosure: Kochenderfer reports research funding from Bluebird Bio Inc. Williams reports a research agreement with Bluebird Bio Inc. for projects unrelated to those discussed in this article. Biffi, Daley and Ferrua report no relevant financial disclosures.

 

 

Is gene therapy likely to become a standard of care for hematologic disorders?

Yes.

The scientific and clinical development of gene therapy for hematologic diseases have many similarities to the rocky pathway bone marrow transplantation (BMT) experienced during the 1950s through 1970s, with gene therapy currently positioned where BMT was in the late 1970’s. Dirk van Bekkum, MD, a pioneer in experimental transplantation, in 1967 said that the repeated clinical failures of BMT in the 1950s and 1960s occurred “mainly because the clinical applications were undertaken too soon, most of them before even the minimum basic knowledge required to bridge the gap between mouse and patient had been obtained.” Luckily, he and many others persevered, and their passion was vindicated by the accumulation of clinical successes during the 1980s and 1990s, linked to increased understanding of human immunology, better drugs to prevent rejection and graft-versus-host disease, and deeper insights into underlying target disease pathophysiology.

Gene therapy jumped from concept to prototype, integrating murine viral-based gene transfer vectors to early clinical trials very rapidly between the mid-1980s and 1990s, and all of van Bekkum’s comments on early BMT failures apply tore early clinical gene therapy trial setbacks. Gene therapy investigators, including myself, were working in the dark regarding basic biology of target cell populations such as hematopoietic stem cells; had only rudimentary knowledge of the genome with little knowledge of regions outside a small number of sequenced gene exons; lacked predictive preclinical models; and relied on first-generation integrating viral vectors that had not yet been optimized and were very poorly understood. One wishes we had learned more from the experiences of early BMT pioneers and not let enthusiasm for the elegance of the concept of curative gene therapy for hematopoietic disorders get ahead of knowledge, but the lack of effective treatments for fatal diseases such as X-linked severe combined immunodeficiency (SCID-X1) pushed the field forward into the first clinical trials. Despite lack of clinical benefit, the lessons learned certainly contributed to insights into safety and feasibility and pointed the way forward.

Over the past 5 to 10 years, gene therapy has rapidly matured, both scientifically and clinically. There is no question that patients with hemophilia B, SCID-X1 and other inherited immunodeficiencies, thalassemia and, most strikingly, CD19-positive lymphoid malignancies have benefited from gene therapy. I would even suggest that lentiviral gene addition of a corrective gene to autologous CD34-positive cells followed by transplantation is close to reaching standard-of-care status for patients with severe rare immunodeficiency disorders who have no appropriate allogeneic transplantation options, as well as those who have failed transplant.

Many questions remain regarding the path to making various gene therapy approaches commercially and practically feasible beyond small investigator-sponsored clinical trials at academic medical centers. However, based on compelling recent gene therapy clinical successes in hematologic and nonhematologic diseases, the venture capital sector has poured billions of dollars into startups capitalizing on these successes. Rapid maturation to successful public offerings have occurred even for small new gene therapy companies — for instance Spark Therapeutics, founded by Katherine A. High, MD, an ASH member and hematologist who pioneered gene therapy for hemophilia, has a market capitalization of $1.6 billion.

The “big pharma” sector has jumped into the field aggressively in the past year, with Bayer AG, GlaxoSmithKline, Celgene and Novartis setting up partnerships with gene therapy biotechnology firms or initiating their own internal gene therapy programs. The first gene therapy marketing approval occurred last year by the European Medicines Agency for alipogene tiparvovec (Glybera, uniQure), a gene therapy treatment for lipoprotein lipase deficiency. There are almost 500 gene therapy products in the pipeline. Creative payment strategies such as annuities are being proposed to cover very large initial costs for a curative therapy that, nonetheless, may be much cheaper in the long run than lifelong care for debilitating chronic disorders such as hemophilia or sickle cell anemia.

Even more powerful technologies for actual targeted gene knockout or gene editing are in active development, most notably zinc finger nucleases that are already showing promise in clinical trials for HIV, and CRISPR/Cas9 strategies that are even more efficient, simple and specific. The clinical applications for these approaches are much broader than gene addition, allowing treatment of disorders linked to expression of abnormal gene products instead of only those resulting from loss of a gene product. The future for gene therapy finally seems bright, and both scientific and clinical advances continue to be featured at the ASH Annual Meeting and Exposition. As the incoming president of American Society for Gene and Cell Therapy, it has been personally heartening to see markedly increased interest in our field after almost 30 years of involvement in the field both scientifically and clinically.

 

References:

Rivière I, et al. Blood. 2012;doi:10.1182/blood-2011-09-349993.

Wirth T, et al. Gene. 2013;doi:10.1016/j.gene.2013.03.137.

Cynthia E. Dunbar, MD, is head of the molecular hematopoiesis section in the hematology branch of the NHLBI, as well as president-elect of the American Society for Gene and Cell Therapy. She can be reached at dunbarc@nhlbi.nih.gov. Disclosure: Dunbar reports no relevant financial disclosures.

No.

There are many reasons for the excitement surrounding gene therapy from hematologists and oncologists. Gene therapy for hereditary disorders — what we usually call benign hematology — that often affect pediatric patients allows doctors to target the abnormalities directly and reverse it. That is exciting, because some of these diseases can be truly eradicated through this method; as physicians, we are usually only able to treat something and suppress it — which enables patients to live with it — or to provide therapy. Here, we have mutations that can be fixed directly.

In the world of adult hematology and blood cancer, there is also excitement about the possibility of moving away from the blind and blunt instrument of cytotoxic chemotherapy, which introduces the potential for a lot of potential long-term adverse events without really attacking the cancer. Gene-modified T cells or natural killer cells can harness our immune system to fight cancer, which could be a new paradigm in our field.

However, it is important to recognize that barriers still exist before gene therapy can be widely considered a standard of care in hematology. These procedures require a lot of expertise, meaning they can only be done at academic centers at this time. Processing stem cells and engineering the product cannot be done without a high level of specialized knowledge and experience. Because much of cancer care takes place in the community medical setting, this is a clear barrier to patients who are unable to travel to academic hospitals for their treatment.

Safety concerns also remain for the treatment of hematologic malignancies with gene therapy. Cytokine release syndrome has frequently been seen in these patients; at times, it has been lethal. A lot of patients experience significant toxicities, requiring intensive care input. This still needs to be addressed, and we should be working to develop safer ways to administer the therapy.

Chimeric antigen receptor T cells are an area of great interest in gene therapy, but questions remain about the persistence of these T cells. At this time, it might be that the T cells can only be found for a few weeks, whereas we need them to persist for much longer to prevent cancer recurrence. Production time is a huge issue. Stephen J. Schuster, MD, and colleagues presented a study at the ASH Annual Meeting and Exposition in December about the use of gene therapy for aggressive B-cell malignancies. Of the 26 patients enrolled, only 15 were able to be infused with a product. By the time the product was available, four of those patients had already progressed. Six patients on the study also experienced production failure, which suggests this area still needs some work.

Gene therapy holds great potential for hematology, but more work still needs to be done.

 

Reference:

Schuster SJ, et al. Abstract 183. Presented at: ASH Annual Meeting and Exposition; Dec. 5-8, 2015; Orlando, Fla.

Stefan K. Barta, MD, MS, MRCP(UK), is assistant professor of hematology and oncology at Fox Chase Cancer Center. He can be reached at stefan.barta@fccc.edu. Disclosure: Barta reports no relevant financial disclosures.