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Clinical Cancer Research Vol. 5, 1319-1323, June 1999
© 1999 American Association for Cancer Research

Clinical Trials

Long Survival of Patients with Small Cell Lung Cancer after Adjuvant Treatment with the Anti-Idiotypic Antibody BEC2 Plus Bacillus Calmette-Guérin1

Stefan C. Grant2, Mark G. Kris, Alan N. Houghton and Paul B. Chapman

Thoracic Oncology Service, Division of Solid Tumor Oncology [S. C. G., M. G. K.], and Clinical Immunology Service, Division of Hematology [A. N. H., P. B. C.], Department of Medicine, Memorial Sloan-Kettering Cancer Center and Joan and Sanford I. Weill Medical College of Cornell University, New York, New York 10021


   ABSTRACT
Top
 ABSTRACT
INTRODUCTION
 PATIENTS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
Despite active therapies for small cell lung cancer (SCLC), most patients relapse and die of the disease. The present study evaluates immunization using the anti-idiotypic antibody BEC2, which mimics the ganglioside GD3 expressed on the surface of most SCLC tumors, combined with Bacillus Calmette-Guérin (BCG) as an immune adjuvant. We hypothesized that active immunization could alter the natural history of the disease. Fifteen patients who had completed standard therapy for SCLC received a series of five intradermal immunizations consisting of 2.5 mg of BEC2 plus BCG over a 10-week period. Blood was collected for serological analysis, and outcome was monitored. All patients developed anti-BEC2 antibodies, despite having received chemotherapy with or without thoracic radiation. We detected anti-GD3 antibodies in five patients, including those with the longest relapse-free survival. The median relapse-free survival for patients with extensive stage disease is 11 months and has not been reached for patients with limited stage disease (>47 months), with only one of seven patients having relapsed after a median follow-up of 47 months. Immunization of patients with SCLC after standard therapy using BEC2 plus BCG can induce anti-GD3 antibodies and is safe. The survival and relapse-free survival in this group of patients are substantially better than those observed in a prior group of similar patients. A Phase III trial is being conducted to evaluate BEC2 plus BCG as adjuvant therapy after chemotherapy and irradiation.


   INTRODUCTION
Top
 ABSTRACT
 INTRODUCTION
PATIENTS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
SCLC3 is the fifth most common cause of cancer death in the United States; each year, almost 40,000 new cases are diagnosed, and the majority of patients will die of the disease (1) . In the early 1970s, chemotherapy with or without radiation therapy produced substantial improvements in the median survival of patients with this disease. However, since then, there have not been any major advances (2) . Despite high response rates including complete response rates, most patients relapse and die. Neither increased doses of chemotherapy nor prolonged treatment has been proven to be of benefit. We hypothesized that using optimal chemotherapy with or without radiation therapy to achieve a maximal antitumor effect followed by an immunological modality such as active immunization could eliminate microscopic residual disease and improve survival.

The ganglioside GD3 is a cell surface glycosphingolipid antigen with limited expression in normal tissues, being largely restricted to cells of neuroectodermal origin and to a subset of T lymphocytes 3, 4, 5, 6, 7) . Most SCLC tumors and cell lines express GD3 (8) .4 Our experience in melanoma indicated that ganglioside GD3 would be an appropriate antigenic target for immunological therapy in GD3-positive tumors (9) , and this was supported by our experience in immunizing melanoma patients against GD3 using the anti-idiotypic antibody BEC2, a mouse IgG2b anti-idiotypic antibody that structurally mimics GD3 (10) . For these reasons, we undertook a trial in SCLC patients. BEC2 was combined with BCG because experience in the melanoma system indicated that a potent immune adjuvant was required to induce an immune response against GD3.

The objectives of the trial were as follows: (a) to study the toxicity and feasibility of immunizing SCLC patients with BEC2 plus BCG after achieving a major objective response to standard therapy; (b) to determine whether immunization with BEC2 combined with BCG results in a humoral response directed against the GD3 ganglioside in such patients after chemotherapy with or without radiation; and (c) to observe the overall survival and relapse-free survival of patients receiving this treatment.


   PATIENTS AND METHODS
Top
 ABSTRACT
 INTRODUCTION
 PATIENTS AND METHODS
RESULTS
 DISCUSSION
 REFERENCES
 
Patients with pathologically confirmed SCLC who had completed initial therapy and who had achieved a partial or complete response by WHO criteria (11) without subsequent relapse or progression were eligible for the study. Prior to entry, computed tomography of the chest was performed, and the sites of disease identified at the time of diagnosis were reevaluated. At least 1 month between the completion of therapy and the initiation of protocol treatment was required, and patients were required to have a WBC count of >=3500 cells/mm3 . Patients with clinically significant heart disease (New York Heart Association Class III or IV) or other serious intercurrent illnesses, including active infections requiring antibiotics or a known immunodeficiency, were excluded. While receiving immunizations, the use of antihistamines, nonsteroidal anti-inflammatory drugs, or corticosteroids was not permitted. Patients who had previously received mouse antibody injections were also ineligible.

Treatment consisted of a series of five immunizations of BEC2 plus BCG administered intradermally on weeks 0, 2, 4, 6, and 10. BEC2 was combined with reconstituted BCG (TheraCys; Connaught Laboratories, Inc., Swiftwater, PA) before administration. For each patient, the first immunization consisted of 2.5 mg of BEC2 combined with 2 x 107 CFU of BCG. The mixture was then administered in a series of intradermal injections in one limb. Subsequent immunizations were administered in different limbs. During the course of immunization, the dose of BEC2 remained at 2.5 mg, whereas the dose of BCG administered was reduced for each subsequent dose: 3 x 106 CFU/immunization on week 2; 1 x 106 CFU/immunization on week 4; 3 x 105 CFU/immunization on week 6; and 1 x 105 CFU/immunization on week 10. Blood samples were collected before the initiation of treatment and then collected every 2 weeks for a total of 12 weeks. Patients were required to receive at least four immunizations to be evaluable for serological response. Determination of serum titers of anti-BEC2 (human antimouse antibody HAMA) and anti-GD3 titers were determined by ELISA as described previously (10) . A positive anti-GD3 antibody response in a patient was defined as at least a 4-fold increase in anti-GD3 titer in at least two separate serum samples compared to the patient’s preimmune serum. Overall survival, time to relapse, and disease-free survival were measured by the method of Kaplan and Meier (12) . The survival analysis was performed on an "intent to treat" basis that included one patient who relapsed after three immunizations.

Patient Characteristics.
A total of 15 patients were entered on study. At the time of their diagnosis, eight patients had extensive stage disease, and seven had limited stage disease. There were eight men and seven women, with a median age of 61 years (range, 42–73 years) and a median Karnofsky performance status of 80% (range, 70–90%). Two patients with limited stage disease and one patient with extensive stage disease presented with hyponatremia, and one patient with limited stage disease and four patients with extensive stage disease had elevated serum lactate dehydrogenase at diagnosis. All patients were treated with standard chemotherapy regimens; the majority were treated with a combination of cisplatin plus etoposide. Other drugs administered included cyclophosphamide, doxorubicin, and carboplatin. All patients with limited stage disease received thoracic radiation. Eleven patients had partial responses, and four patients had complete responses by WHO criteria after the completion of standard therapy. The median time from initiation of treatment to completion of standard therapy was 5.4 months (range, 3.5–11 months).


   RESULTS
Top
 ABSTRACT
 INTRODUCTION
 PATIENTS AND METHODS
 RESULTS
DISCUSSION
 REFERENCES
 
Adverse effects were generally mild. Systemic effects were limited to occasional mild fevers (grade 1) in the first 24 h after an immunization. The major toxicity, which was expected and occurred in all patients, was a local skin reaction to the BCG component of the vaccine. One patient experienced grade 2 and 14 patients experienced grade 3 local skin toxicity. Induration, ulceration, and some discomfort were seen at all immunization sites in these patients, albeit less severe with decreasing doses of BCG. The ulcerations resolved without any treatment, and no patient failed to complete the study because of an adverse effect.

All patients developed anti-BEC2 antibodies (HAMA). Of the 13 patients evaluable for a serological response, 5 developed measurable anti-GD3 antibody responses. All of them developed measurable IgM anti-GD3 antibodies; 3 patients also developed IgG antibodies (Fig. 1)Citation . Peak titers ranged from 1:80 to 1:320, consistent with our previous results in melanoma patients (10) . We did not measure the duration of anti-GD3 titers in most patients, but in at least one patient, anti-GD3 antibodies were detectable after 1 year (data not shown). However, the anti-GD3 response was short-lived in some patients (Fig. 1C)Citation .



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  		Fig. 1. Anti-GD3 antibody responses are induced by BEC2 plus BCG. Anti-GD3 antibodies were measured by ELISA as described previously (10) . The end point titer was defined as the highest serum dilution resulting in an absorbance reading >=0.05 at 405 nm. Arrows indicate immunization with BEC2/BCG. A—E represent each of the five patients who developed anti-GD3 antibody responses. Both IgG () and IgM (•) titers are shown except for the patient represented in D. IgG analysis gave unacceptably high background readings in this patient, therefore only IgM results are reported.

 
Median overall survival was measured from the time of diagnosis and was 20.5 months (Fig. 2)Citation , with the longest relapse-free intervals being observed in the patients with measurable anti-GD3 antibodies (see Table 1Citation ). The median time to relapse was 10.6 months for those patients with extensive stage disease at the time of diagnosis and, with a median follow-up of 47 months from diagnosis, has yet to be reached for the patients with limited stage disease. Three patients have died from causes other than SCLC. One patient with limited stage disease died from respiratory failure related to severe chronic obstructive pulmonary disease and pneumonia 20 months after his diagnosis. A second patient with limited stage disease died as a result of non-SCLC 5 years after the diagnosis of SCLC. A third patient with extensive stage disease died as a result of a motor vehicle accident 19 months after diagnosis. An autopsy failed to demonstrate any evidence of SCLC. One patient with extensive stage disease was found to have developed brain metastases 6 weeks after completion of her immunization. After receiving whole brain radiation therapy, she remains free of SCLC 52 months later, and, more than 5.5 years after her diagnosis, she is alive with non-SCLC. Pathological review of the two patients with non-SCLC confirmed that these were indeed new second primary lung cancers. Kaplan-Meier analysis of relapse-free survival is shown in Fig. 2Citation .



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  		Fig. 2. Kaplan-Meier plot of relapse-free survival of patients treated with BEC2 plus BCG. Overall relapse-free survival and relapse-free survival according to stage is shown. One patient with extensive stage disease developed brain metastases 10.6 months after diagnosis, was treated with whole brain radiation therapy, and remains progression free 52 months later (>5 years after diagnosis). The patient is treated as having relapsed at 10.6 months in the Kaplan-Meier analysis.

 

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  		Table 1 Time from diagnosis to relapse or progression correlated with the development of detectable anti-GD3 antibodies

 
Using an "intent to treat" approach that included the one patient who did not complete immunization, the survival of the patients treated with BEC2 plus BCG was compared to a control group consisting of the 31 of 100 patients entered into the last Phase III SCLC trial conducted at Memorial Sloan-Kettering Cancer Center who had completed therapy on the prior trial and who met the eligibility criteria of the present trial. The control group was representative of SCLC patients reported in the literature. No significant differences were identified in the prognostic criteria of the group, nor did the survival of the control group differ from that of a group of patients entered into a published adjuvant trial (Ref. 13 ; selected because the authors reported survival from the time of diagnosis). Nevertheless, the patients who were treated with BEC2 plus BCG had an overall survival (Fig. 3)Citation and relapse/progression-free survival that were far longer than expected.



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  		Fig. 3. Kaplan-Meier plots of overall survival of patients treated with BEC2 plus BCG compared to the Memorial Sloan-Kettering Cancer Center historical group. The BEC2 plus BCG group includes three patients who died of causes other than SCLC.

 

   DISCUSSION
Top
 ABSTRACT
 INTRODUCTION
 PATIENTS AND METHODS
 RESULTS
 DISCUSSION
REFERENCES
 
Previous attempts to immunize patients with GD3 have been unsuccessful due to its limited immunogenicity in humans. (14) We explored an alternative approach using BEC2, an anti-idiotypic monoclonal antibody that mimics the ganglioside GD3 (15) . As a xenogeneic protein, BEC2 is more immunogeneic than the ganglioside GD3. In both preclinical studies and patients with melanoma, BEC2 was able to induce the development of anti-GD3 antibodies (16) . A series of clinical trials demonstrated that the addition of BCG as an immune adjuvant resulted in an improved immune response to BEC2 (10) .

The present study demonstrated the feasibility of immunizing patients with SCLC after treatment with chemotherapy and radiation therapy, using a 10-week schedule derived from our prior experience in immunizing patients with melanoma against ganglioside antigens. Despite concerns by many investigators that prior chemotherapy and/or radiotherapy would result in immunosuppression, there are little data to support this. Using rigorous criteria for a positive response, all patients developed anti-mouse antibodies, and 5 of 13 patients evaluable for a serological response were shown to have a positive anti-GD3 antibody response. This is similar to our previous observations in melanoma patients who had never received treatment, in which BEC2 plus BCG induced measurable serological responses in 20% of patients (10) , and suggests that there is no measurable humoral immune suppression in these patients. Four of the five patients with positive antibody responses have had the longest systemic relapse-free survival. Patients without measurable anti-GD3 antibody responses have also had long relapse-free survivals, possibly reflecting the limitations of the assays used. Systemic antibody levels below those measured in our assays may be sufficient to provide an antitumor effect. The dose-response relationship between anti-GD3 antibodies remains unclear, and antitumor responses as threshold titers for antitumor effects have not been confirmed for any human tumor system. It is interesting to note that in passive immunotherapy trials using the mouse anti-GD3 antibody R24, antimelanoma effects occurred at lower doses rather than at higher doses (9) . Alternatively, there may be other immune effector mechanisms at play. The role of cellular immunity also remains unresolved.

Overall, the treatment was well tolerated; the only significant toxicity was the local skin reaction to immunization with live BCG, which was self-limited. Although most patients experienced skin ulceration, this was self-limiting in all cases and neither interfered with the patient’s activities nor required treatment. Despite the fact that GD3 is expressed on some normal tissues, there was no evidence that there was any toxicity related to an immune response against these tissues.

Conclusion.
To date, despite an ever-growing number of highly active chemotherapeutic agents for SCLC, neither increasing doses nor duration of therapy has altered the cure rate over the past two decades, and most patients continue to die of this disease. In an attempt to improve these results, investigators have explored the use of immunological therapies, including the use of BCG, without apparent benefit (17, 18, 19) . The data from our study suggest that immunization with BEC2 plus BCG may be an effective means to eliminate residual disease not destroyed by conventional chemotherapy and radiation therapy. Notwithstanding the limited power of the present study, six of seven patients with limited stage SCLC remain free of progression 12–69 months after diagnosis, with a median follow-up of 47 months. To further explore the effects of BEC2/BCG vaccine, a Phase III trial entitled "Survival in an International Phase III Prospective Randomized Limited Disease SCLC Vaccination Study with Adjuvant BEC2 and BCG (SILVA)" is under way to evaluate, in a randomized prospective manner, the role of BEC2 plus BCG as an adjuvant therapy after completion of standard treatment for SCLC.


   ACKNOWLEDGMENTS
 
We thank Damian Martino, Michael Cohen, and Lucy Dantis, R.N., for assistance in the conduct of the trial.


   FOOTNOTES
 
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

1 Supported in part by NIH Grant CA-33409, the Swim Across America Foundation, the Louis and Anne Abrons Foundation, the American Cancer Society, and Imclone Systems, Inc. Back

2 To whom requests for reprints should be addressed, at Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021. Phone: (212) 639-5126; Fax: (212) 794-4357. Back

3 The abbreviations used are: SCLC, small cell lung cancer; BCG, Bacillus Calmette-Guérin; CFU, colony-forming unit. Back

4 S. C. Grant, unpublished observations. Back

Received 11/30/98; revised 2/ 2/99; accepted 2/11/99.


   REFERENCES
Top
 ABSTRACT
 INTRODUCTION
 PATIENTS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 

  1. Landis S. H, Murray T, Bolden S, Wingo P. A. Cancer statistics. CA Cancer J. Clin., 48: 6-29, 1998.[Abstract]
  2. Chute J. P, Venzon D. J, Hankins L, Okunieff P, Frame J. N, Ihde D. C, Johnson B. E. Outcome of patients with small-cell lung cancer during 20 years of clinical research at the US National Cancer Institute. Mayo Clin. Proc., 72: 901-912, 1997.[Medline]
  3. Zhang S, Cordon-Cardo C, Zhang H, Reuter V, Adluri S, Hamilton W, Lloyd K, Livingston P. Selection of tumor antigens as targets for immune attack using immunohistochemistry. I. Focus on gangliosides. Int. J. Cancer, 73: 42-49, 1997.[Medline]
  4. Graus F, Cordone-Cardo C, Houghton A. N. Distribution of the ganglioside GD3 in the human nervous system detected by R24 mouse monoclonal antibody. Brain Res., 324: 190-194, 1984.[Medline]
  5. Dippold W, Dienes H, Knuth A, Meyer zum Buschenfeld K. Immunohistochemical localization of ganglioside GD3 in human malignant, epithelial, and normal tissues. Cancer Res., 45: 3699-3705, 1985.[Abstract/Free Full Text]
  6. Dippold W, Lloyd K, Li L, Ikeda H, Oettgen H, Old L. Cell surface antigens of human malignant melanoma: definition of six antigenic systems with mouse monoclonal antibodies. Proc. Natl. Acad. Sci. USA, 77: 6114-6118, 1980.[Abstract/Free Full Text]
  7. Welte K, Miller G, Chapman P. B, Yuasa H, Natoli E, Kunicka J. E, Cordon-Cardo C, Buhrer C, Old L. J, Houghton A. N. Stimulation of T cell lymphocyte proliferation by monoclonal antibodies against GD3 ganglioside. J. Immunol., 139: 1763-1771, 1987.[Abstract]
  8. Fuentes R, Allman R, Mason M. D. Ganglioside expression in lung cancer cell lines. Lung Cancer, 18: 21-33, 1997.[Medline]
  9. Nasi M, Meyers M, Livingston P, Houghton A, Chapman P. Anti-melanoma effects of R24, a monoclonal antibody against GD3. Melanoma Res., 7 (Suppl. 2): S155-S162, 1997.
  10. McCaffery M, Yao T-J, Williams L, Livingston P. O, Houghton A. N, Chapman P. B. Immunization of melanoma patients with BEC2 anti-idiotypic monoclonal antibody that mimics GD3 ganglioside: enhanced immunogenicity when combined with adjuvant. Clin. Cancer Res., 2: 679-686, 1996.[Abstract]
  11. WHO Handbook for Reporting Results of Cancer Treatment WHO Geneva 1979.
  12. Kaplan E. L, Meier P. Nonparametric estimation from incomplete observations. J. Am. Stat. Assoc., 53: 457-481, 1958.
  13. Mattson K, Niiranen A, Pyrhonen S, Holsti L. R, Holsti P, Kumpulainen E, Cantell K. Natural interferon {alpha} as maintenance therapy for small cell lung cancer. Eur. J. Cancer, 28A: 1387-1391, 1992.
  14. Ritter G, Boosfeld E, Adluri R, Calves M, Oettgen H. F, Old L. J, Livingston P. O. Antibody response to immunization with ganglioside GD3 and GD3 congeners (lactones, amide and gangliosidol) in patients with malignant melanoma. Int. J. Cancer, 48: 379-385, 1991.[Medline]
  15. Chapman P. B, Houghton A. N. Induction of IgG antibodies against GD3 in rabbits by an anti-idiotypic monoclonal antibody. J. Clin. Investig., 88: 186-192, 1991.
  16. Chapman P. B, McCaffery M, Zuklys K, Giorgio N, Houghton A. N. Immunization with BEC2 anti-idiotypic monoclonal antibody that mimics GD3 ganglioside: superiority of the intravenous route. Proc. Am. Assoc. Cancer Res., 36: 493 1995.
  17. McCracken J. D, Heilbrun L, White J, Reed R, Samson M, Saiers J. H, Stephens R, Stuckey W. J, Bickers J, Livingston R. Combination chemotherapy, radiotherapy, and BCG immunotherapy in extensive (metastatic) small cell carcinoma of the lung: a Southwest Oncology Group Study. Cancer (Phila.), 46: 2335-2340, 1980.[Medline]
  18. McCracken J. D, Chen T, White J, Samson M, Stephens R, Coltman C, Saiki J, Lane M, Bonnet J, McGavran M. Combination chemotherapy, radiotherapy, and BCG immunotherapy in limited small-cell carcinoma of the lung: a Southwest Oncology Group study. Cancer (Phila.), 49: 2252-2258, 1982.[Medline]
  19. Jackson, D. V., Paschal, B. R., Ferree, C., Richards, F., Muss, H. B., Cooper, M. R., White, D. R., Stuart, J. J., Spurr, C. L., Wells, B., Sartiano, G., McFarland, J., and McCulloch, J. Combined chemotherapy-radiotherapy with and without the methanol-extraction residue of bacillus Calmette-Guéerin (MER) in small cell carcinoma of the lung. Cancer (Phila.), 50: 48–52, 1982. 5126; Fax (212) 794-4357.



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