Pathologic Validation of Deauville Score-Based Disease on F-18 FDG PET/CT after First-Line Treatment in Patients with Lymphoma.

Purpose: PET/CT-based Deauville scoring (DS) is routinely used for lymphoma response assessment. However, pathological correlation of DS is not yet precisely documented. In the present study we aimed to pathological confirm the PET/CT-based Deauville scoring (DS) in lymphoma after first-line chemotherapy. Materials and methods: Participants undergoing PET/CT for response assessment following first-line treatment were recruited prospectively. DS ≥ 4 lesions were interpreted as PET-positive, while DS ≤ 3 as PET-negative. Participants with a PET-positive lesion or suspicious of inadequate response (DS ≤ 3) were recruited for metabolic core-needle biopsy. True-negative and benign histopathology were kept on follow-up for three months. Histopathological, clinical and imaging findings were assessed for diagnostic performance. Procedure-related complications were also noted. Results: In all, 148/480 participants were PET-positive, and 332/480 were PET-negative. 138/148 PET-positive and 12/332 PET-negative lesions were recruited for biopsy. Biopsy was performed in 147/150 participants (PET-positive 135; PET-negative 12). Three patients with inaccessible lesions were excluded. The diagnostic yield of the procedure was 97.3% (143/147). Histology revealed lymphoma in 106 participants (including 70% of total DS-4, 100% of DS-5a and 73.9% of DS-5b lesions), with three false-negative lesions. DS ≤ 3 lesions were true-negative except one diagnosed with lymphoma (8.3%) on follow-up. Non-lymphomatous malignancies (n = 5), granulomas (n = 12), non-specific inflammation (n = 9) and no residual disease (n = 11) were diagnosed in the rest. No major procedure-related adverse event was noted. Conclusion: A DS-5a lesion suggests residual disease; hence, a biopsy can be prevented unless Richter's transformation is suspected. DS-4 and DS-5b lesions require a biopsy before changing the treatment plan, as a certain number of participants had non-lymphomatous F-18 FDG-avid lesions.

Characterisation of novel KIR alleles: KIR3DL3*0070105, KIR3DL3*0130202, KIR3DL1*0080104 and KIR3DL1*0010121.

KIR3DL3*0070105, KIR3DL3*0130202, KIR3DL1*0080104 and KIR3DL1*0010121, identified by next generation sequencing in individuals from India.

Randomized controlled trial of pre-transplant zoledronate versus observation for prevention of bone loss in allogeneic hematopoietic cell transplantation.

Background: Approximately half of allogeneic hematopoietic cell transplantation (HCT) recipients experience significant bone loss in the early post-HCT period. Only recently have international guidelines started recommending early screening. However, the guidance for intervention remains conservative. In this study, we sought to evaluate the efficacy of pre-transplant prophylactic zoledronate in preventing early bone loss in allogeneic HCT recipients. Methods: This was an open-label, investigator-initiated, phase 2 randomized controlled trial (RCT) of prophylactic zoledronate versus observation to prevent bone loss in allogeneic HCT recipients. Recipients aged ≥ 18 years of age were included after informed consent and randomized to prophylactic zoledronate 4 mg pre-HCT or observation in a 1:1 ratio. The primary outcome of the study was bone mineral density (BMD) loss at the femoral neck (FN), total hip (TH), and lumbar spine (LS), as assessed using dual-energy X-ray absorptiometry (DXA) on day+100 post-HCT. The secondary outcomes included BMD loss on day+365 and Z scores on day+100 and day+365 at the FN, TH, and LS sites. Results: The trial was terminated because the interim analysis showed a significant benefit in the intervention arm, with 50% planned recruitment. A total of 40 patients were randomized to the zoledronate and control arms. Both arms were matched for age, sex, diagnosis, pre-HCT steroid exposure, body mass index, human leukocyte antigen (HLA) match, and conditioning intensity. The grade 2-4 acute graft versus host disease (GVHD) incidences were comparable. The primary endpoint of BMD loss at FN and TH at day+100 was significant (5.62% vs. -6.78%, p = 0.009, -1.59 vs. -3.98, p = 0.016, respectively). There was no difference in the secondary endpoint of BMD loss on day+365 compared to that on day+100 or baseline at any BMD site. There was no difference in the Z-scores at any site on day+100 or day+365. Conclusions: Prophylactic zoledronate prevented early bone loss on day+100. The indicated preemptive zoledronate beyond day+100 in recipients prevented further bone loss. Patients receiving prophylactic zoledronate may benefit from a supplementary dose of the indicated preemptive zoledronate.

Non-invasive Estimation of Microvasculopathy & Endothelial Dysfunction in Stem Cell Transplant Recipients and its Relationship with GVHD.

Introduction: Microvasculopathy and endothelial dysfunction play important roles in the development of post-transplant complications, including graft-versus-host disease (GVHD). We assessed structural microvasculopathy by employing nailfold video capillaroscopy (NFVC) and endothelial dysfunction via flow-mediated dilatation (FMD) of the brachial artery in recipients of hematopoietic stem cell transplantation. Patients and methods: Recipients of stem cell transplantation were included in this study post day+100 and divided into two cohorts. The first cohort consisted of 35 recipients of allogeneic hematopoietic stem cell transplantation (HCT) and the second cohort was comprised of 31 recipients of autologous HCT. A third cohort included 35 healthy individuals. NFVC was conducted on the second to fifth fingers of both hands using an Optilia video capillaroscope at 200× magnification, and the images were analyzed according to the European Alliance of Associations for Rheumatology (EULAR) criteria. The following parameters were used to measure vasculopathy: (a) median capillary density, derived from the capillary density of eight fingers, (b) median capillary diameter, derived from maximum capillary apical diameters of eight fingers, and (c) significant neoangiogenesis (neoangiogenesis present in ≥2 fingers). FMD of the right brachial artery was observed by high-resolution ultrasonography using the principle of post-occlusive reactive hyperemia, and video images were analyzed using edge-detecting software. Results: The median capillary diameter was significantly higher in the allo-HCT cohort (20.56±5.17 micrometer) compared to the auto-HCT cohort (16.19±3.31 micrometer; p<0.001) and healthy controls (14.66±2.61 micrometer; p<0.001). The median capillary density was significantly lower in the allo-HCT cohort (median: 6 capillaries/mm, range: 5-9 capillaries/mm) compared to the auto-HCT cohort (median: 8.5 capillaries, range: 5-12 capillaries/mm; p<0.001) and healthy controls (median: 8 capillaries/mm, range: 7-10.5 capillaries/mm; p<0.001). The allo-HCT cohort had a higher proportion of patients with significant neoangiogenesis (86%) than the auto-HCT cohort (10%) and healthy controls (9%). The presence of significant neoangiogenesis was more frequent in the subgroup of patients with a history of GVHD (93%) compared to the subgroup of patients without any history of GVHD (57%; p=0.044). No significant differences in NFVC parameters or FMD were observed between recipients of myeloablative and reduced-intensity conditioning regimens. There was no significant difference in NFVC parameters between the auto-HCT cohort and healthy controls. There was no significant difference in FMD among the three cohorts; however, a higher proportion of patients in the allo-HCT cohort (28%) had lower FMD than those in the auto-HCT cohort (3%) and healthy controls (6%), suggesting endothelial dysfunction. Conclusions: Our findings demonstrate the presence of structural microvasculopathy in allo-HCT recipients and suggest a possible role of alloreactivity in the pathogenesis of post-HCT microvasculopathy.

Flow cytometric expression of Bcl-2, Mcl-1, and their ratios correlates with primary and secondary cytogenetic changes and their combinations in multiple myeloma.

Response to BH3 mimetics in multiple myeloma (MM) correlates with CCND1-rearrangement or expression of anti-apoptotic molecules, particularly Bcl-2 and Mcl-1. Our study investigates the relationship between cytogenetic abnormalities (CGAs) and intracellular Bcl-2 and Mcl-1 expression in myeloma plasma cells (MPCs) using flow cytometry (FCM). We measured median fluorescence intensity (MFI) of Bcl-2 and Mcl-1 in 163 bone marrow samples (143 MM, 20 controls) across various cell types. Both Bcl-2MFI and Mcl-1MFI were significantly higher in MPCs compared to other cells, with Bcl-2 MFI exceeding Mcl-1 MFI in MPCs. Bcl-2 expression peaked in CCND1-rearranged cases, while Mcl-1 expression was highest in cases with 1q21 gain/amplification. Notably, 65-74% of cases with other CGAs exhibited moderate to strong Bcl-2 or Mcl-1 expression, indicating potential utility of BH3 mimetics in this group, while 25% showed dim to absent expression of one or both markers, suggesting potential futility in these patients. Our study highlights FCM's potential for rapid Bcl-2 and Mcl-1 quantification, surpassing traditional methods. We propose that direct measurement of Bcl-2 and Mcl-1 expression in PCs by FCM, combined with cytogenetic characterization, could improve therapeutic decision-making regarding the use of BH3 mimetics in MM, potentially enhancing outcomes and overcoming resistance.

Multiplex PCR for gastrointestinal parasites in stool: Benchmarking against direct microscopy and simplex PCR.

PURPOSE: To develop and validate a multiplex conventional PCR assay to simultaneously detect Cryptosporidium spp., Entamoeba histolytica, and Giardia lamblia in diarrheal samples as a rapid, cost-effective, and sensitive diagnostic tool for prevalent co-infections for improved diagnostic accuracy and efficiency in resource-limited settings. METHODS: Stool samples collected from patients with gastrointestinal symptoms after taking written consent, processed via wet mount, iodine mount, and PCR assays. Cohen's kappa statistical analysis was done to test agreement. RESULT: Among 240 patients, 28.75% showed intestinal protozoa via Microscopy; Single-plex and multiplex PCR demonstrated 100% concordance, detecting 27.9%; confirmed by sequencing. Highest parasite positivity was observed in transplant and immunocompromised patients, with moderate to almost perfect agreement between microscopy and molecular methods. CONCLUSION: Multiplex-conventional PCR offers superior sensitivity and specificity over microscopy and 100% concordance with single-plex PCR, enabling rapid, cost-effective diagnosis of multiple parasites from single stool sample. Its adoption could revolutionize parasitic infection management in routine diagnostics.

Identification of four novel KIR alleles in haematopoietic stem cell donors of Indian origin.

Four novel KIR alleles KIR3DL1*0010120, KIR3DS1*01315, KIR3DL3*0020703 and KIR2DL4*0010310 identified using next-generation sequencing.

Coexistence of BCR∷ABL1 translocation and JAK2V617F mutations in indian patients with myeloproliferative neoplasms: A case series.

ABSTRACT: BCR∷ABL1 translocation and JAK2V617F mutations are canonical variants of myeloproliferative neoplasms (MPNs). Traditionally considered mutually exclusive, they may rarely coexist. We report the clinicopathological profile and treatment outcomes of four MPN patients with coexistence of these disease-defining genetic variants. Both mutations were detected simultaneously in three patients who did not harbor tell-tale signs of CML and were evaluated for both BCR∷ABL1 and JAK2V617F based on clues from hemogram, peripheral-blood and bone-marrow examination. All were treated with imatinib and hydroxyurea and attained major molecular response after 2-7 months. In another patient, JAK2V617F was detected 15 years after the diagnosis of CML at the time of evaluation of loss of hematological and molecular response. She was treated with dasatinib but no hematologic or molecular response was attained after 6 months despite good compliance. In conclusion, BCR∷ABL1 and JAK2V617F may rarely coexist in MPN with variable temporal evolution, clinicopathological profile, and treatment response.

Bridging the gap: understanding contemporary autopsies in acute leukemia by comparing ante-mortem and post-mortem profiles.

This study investigates acute myeloid leukemia/lymphoblastic leukemia (AML/ALL) through a 14-year analysis (2009-2022) of 46 autopsied cases (age >12 years). B-ALL was the dominant subtype (34.8%). Liver and spleen were the common sites of active leukemia (63% cases). Symptoms like dyspnea and altered sensorium associated significantly with heart (p = .031) and brain leukostasis (p = .006). Measurable residual disease (MRD) negativity correlated with disease-free status outside the bone marrow, while MRD-positive cases displayed leukemic infiltrates. Infections were identified in 23 autopsied cases, notably linked to post-induction and post-transplant fatalities. Surprisingly, 18 of these 23 cases had unexpected infections mainly fungal (13 cases) with Aspergillus species as the most common. Diagnostic discrepancies were identified in 48% of cases. Malignant infiltration (46%) and infections (25%) were the leading causes of death. This research sheds light on leukemia in extra-medullary tissues, uncovers novel clinical-pathological associations, and highlights overlooked therapy side effects, offering insights for future case management.

Extramedullary T-lymphoblastic blast crisis in a young male with chronic myeloid leukemia: A rare presentation diagnosed on cytology and flow cytometric immunophenotyping.

BACKGROUND: Extramedullary blast proliferations (EBPs) are known to occur in around 15% of chronic myeloid leukemia (CML) patients in the blast phase. Immunophenotypically, the EBPs are commonly myeloid as compared to the lymphoid. Amongst the lymphoid EBPs, T-lymphoblastic type is considerably rare. Furthermore, the occurrence of EBPs at the initial clinical presentation is extremely rare and such presentations almost always portend the occurrence of an imminent hematological blast crisis shortly. CASE: A 25-year-old male presented with abdominal fullness for 1 month. There was no history of abdominal pain, vomiting, jaundice, weight loss, or night sweats. On clinical examination, the patient was found to have pallor and was febrile. There was hepatosplenomegaly and a single, firm, mobile, left posterior cervical lymph node measuring 1.5 × 1 cm was palpable. Routine blood counts revealed anemia, leukocytosis, and thrombocytopenia. A fine-needle aspiration (FNA) from the cervical revealed T-lymphoid EBP, confirmed by flow cytometry. Subsequently, his bone marrow examination revealed a diagnosis of CML with BCR::ABL1 fusion. Thus, a final diagnosis of CML with extramedullary T-lymphoid blast crisis localized to the cervical lymph node was rendered. CONCLUSIONS: The present report, besides highlighting the utility of FNA cytology in rendering such challenging diagnoses, also reiterates the significance of ancillary techniques, such as flow cytometry, which play a key role in early diagnosis and exact characterization of such rare and aggressive hematolymphoid neoplasms.

Challenges in Administering Salvage Therapy and Outcomes of Relapsed/Refractory Diffuse Large B-Cell Lymphoma Patients: A LMIC Real-World Study.

Standard therapy for patients with Relapsed/Refractory Diffuse Large B-Cell Lymphoma (RR DLBCL) involves salvage chemotherapy followed by autologous hematopoietic stem cell transplant. However, information regarding the number of patients receiving salvage therapy and associated factors is not available from low/middle income countries (LMICs). All patients treated at our center with RR DLBCL from 2016 to 2021 were included in the study. Univariate and multivariate analyses was performed to find factors associated with the lack of receipt of salvage chemotherapy. Eighty-five patients were included in the study. Most patients had primary refractory disease (69.4%). Only 26 patients received standard salvage therapy, while the others (N = 59) received metronomic/palliative oral therapy. On univariate analysis, patients with an annual income below India's Gross National Income per capita (p = 0.014), an education level below Class XII (p = 0.025), Stage III/IV disease at relapse (p = 0.018) and CNS relapse (p = 0.027) were more likely to receive palliative therapy. Conversely, patients with a late relapse were more likely to receive salvage therapy (p = 0.001). On multivariate analysis, patients with Stage III/IV relapse (p = 0.030) and an education level less than Class XII (p = 0.012) were more likely to receive palliative therapy, while patients with a late relapse (p = 0.001) were more likely to receive salvage therapy. Patients who received salvage therapy had a longer Median OS than those who received palliative therapy (p < 0.001). Timing of relapse, stage at relapse and educational status of the patient are significant factors affecting access to effective therapy for patients with RR DLBCL in LMICs.

Plasminogen Activator Inhibitor-1 4G/5G Promoter Polymorphism in Indian Patients with Deep Vein Thrombosis.

A single guanosine deletion/insertion (4G/5G) polymorphism in the promoter region of plasminogen activator inhibitor-1 (PAI-1) gene encoding PAI-1 protein has been investigated in deep vein thrombosis (DVT) patients. The association between PAI-1 4G/5G polymorphism and increased risk of DVT has been reported in some studies, while others have reported a lack of association. The present study aimed to investigate if the PAI-1 4G/5G polymorphism is associated with an increased risk of DVT in the Indian population and to assess its association with thrombophilic risk factors. Fifty-two adult patients with a history of chronic or recurrent DVT and 52 healthy adult controls were genotyped for PAI-1 4G/5G polymorphism. Plasma levels of PAI-1 and other thrombophilic risk factors were also measured. PAI-1 4G/5G polymorphism was not significantly associated with an increased risk of DVT. Protein C deficiency was significantly associated with the 4G/4G genotype. Patients with the 4G/4G genotype had significantly reduced PAI-1 levels as compared to the controls. PAI-1 4G/5G polymorphism did not significantly contribute to an increased risk of DVT in the Indian population. However, in the presence of thrombophilic risk factor abnormalities, the risk of DVT is increased in individuals with the 4G/4G genotype in the Indian cohort. Supplementary Information: The online version contains supplementary material available at 10.1007/s12288-023-01660-3.

Aberrant baseline cytokine profile in patients with newly diagnosed acquired aplastic anaemia correlates with disease severity and the treatment response.

BACKGROUND: Immune dysregulation is crucial in the pathogenesis of acquired aplastic anaemia (aAA). There is paucity of data regarding correlation of baseline cytokine profile with treatment response in aAA. OBJECTIVE: Present prospective case-control study aimed to correlate the baseline cytokines in patients with aAA with the treatment response. METHODS: Fifty-one patients with newly-diagnosed aAA > 13 years of either sex were enrolled over 1.5 years. Twenty age-and sex-matched healthy controls (HC) were also included. The cytokine profile (IL-2, 4, 6, 8, 10, 17, IFN-γ and TNF-α) in the peripheral blood plasma of aAA patients was performed at the baseline using cytometric bead analysis. The cytokine levels were compared with HC and correlated with response to immunosuppressive therapy (IST) at 3-months. RESULTS: The median age of cases was 29 years (range,13-74). The cases had higher mean levels of IL2 (p = 0.326), IL4 (p = 0.038), IL6 (p = 0.000), IL10 (p = 0.002), TNF-α (p = 0.302), IFN-γ (p = 0.569) and IL-17 (p = 0.284) than the HC. The baseline levels of all the cytokines were higher (statistically non-significant) among responders (n = 13) than the non-responders (n = 14) to IST. CONCLUSIONS: Baseline cytokine profile in patients with aAA might predict response to the IST. Larger studies are needed to validate our results.

A multicentre, double-blind, placebo-controlled randomized trial of Mycobacterium w in critically ill patients with COVID-19 (ARMY-2).

BACKGROUND: Mycobacterium w (Mw), an immunomodulator, resulted in better clinical status in severe coronavirus infectious disease 19 (COVID-19) but no survival benefit in a previous study. Herein, we investigate whether Mw could improve clinical outcomes and survival in COVID-19. MATERIALS AND METHODS: In a multicentric, randomized, double-blind, parallel-group, placebo-controlled trial, we randomized hospitalized subjects with severe COVID-19 to receive either 0.3 mL/day of Mw intradermally or a matching placebo for three consecutive days. The primary outcome was 28-day mortality. The co-primary outcome was the distribution of clinical status assessed on a seven-point ordinal scale ranging from discharged (category 1) to death (category 7) on study days 14, 21, and 28. The key secondary outcomes were the change in sequential organ failure assessment (SOFA) score on days 7 and 14 compared to the baseline, treatment-emergent adverse events, and others. RESULTS: We included 273 subjects (136 Mw, 137 placebo). The use of Mw did not improve 28-day survival (Mw vs. placebo, 18 [13.2%] vs. 12 [8.8%], P = 0.259) or the clinical status on days 14 (odds ratio [OR], 1.33; 95% confidence intervals [CI], 0.79-2.3), 21 (OR, 1.49; 95% CI, 0.83-2.7) or 28 (OR, 1.49; 95% CI, 0.79-2.8) between the two study arms. There was no difference in the delta SOFA score or other secondary outcomes between the two groups. We observed higher injection site reactions with Mw. CONCLUSION: Mw did not reduce 28-day mortality or improve clinical status on days 14, 21 and 28 compared to placebo in patients with severe COVID-19. [Trial identifier: CTRI/2020/04/024846].

Extramedullary relapse of multiple myeloma presenting as space-occupying lesion in liver treated with daratumumab, pomalidomide, dexamethasone and bendamustine.

Extramedullary relapse in patients with multiple myeloma (MM) is often associated with loss of biochemical response and the appearance of measurable residual disease in the bone marrow. Fever is an unusual presenting manifestation of MM. Treatment of extramedullary relapse in patients progressing on proteasome inhibitors, anti-CD38 monoclonal antibodies and immunomodulatory drugs is challenging, as access to chimeric antigen receptor T-cells and bispecific antibodies is limited. We report a case of relapsed MM who presented with fever and hepatic space-occupying lesion mimicking hepatocellular carcinoma. In this case report, we also present our experience of using a novel combination regimen comprising Dara-Pom-Benda-Dexa (daratumumab, pomalidomide, dexamethasone and bendamustine) for relapsed MM.

Pharmacogenetic guided versus standard warfarin dosing for routine clinical care with its pharmacoeconomic impact: a randomized controlled clinical trial.

BACKGROUND: Empirical use of pharmacogenetic test(PGT) is advocated for many drugs, and resource-rich setting hospitals are using the same commonly. The clinical translation of pharmacogenetic tests in terms of cost and clinical utility is yet to be examined in hospitals of low middle income countries (LMICs). AIM: The present study assessed the clinical utility of PGT by comparing the pharmacogenetically(PGT) guided- versus standard of care(SOC)- warfarin therapy, including the health economics of the two warfarin therapies. METHODS: An open-label, randomized, controlled clinical trial recruited warfarin-receiving patients in pharmacogenetically(PGT) guided- versus standard of care(SOC)- study arms. Pharmacogenetic analysis of CYP2C9*2(rs1799853), CYP2C9*3(rs1057910) and VKORC1(rs9923231) was performed for patients recruited to the PGT-guided arm. PT(Prothrombin Time)-INR(international normalized ratio) testing and dose titrations were allowed as per routine clinical practice. The primary endpoint was the percent time spent in the therapeutic INR range(TTR) during the 90-day observation period. Secondary endpoints were time to reach therapeutic INR(TRT), the proportion of adverse events, and economic comparison between two modes of therapy in a Markov model built for the commonest warfarin indication- atrial fibrillation. RESULTS: The study enrolled 168 patients, 84 in each arm. Per-protocol analysis showed a significantly high median time spent in therapeutic INR in the genotype-guided arm(42.85%; CI 21.4-66.75) as compared to the SOC arm(8.8%; CI 0-27.2)(p < 0.00001). The TRT was less in the PG-guided warfarin dosing group than the standard-of-care dosing warfarin group (17.85 vs. 33.92 days) (p = 0.002). Bleeding and thromboembolic events were similar in the two study groups. Lifetime expenditure was ₹1,26,830 in the PGT arm compared to ₹1,17,907 in the SOC arm. The QALY gain did not differ in the two groups(3.9 vs. 3.65). Compared to SOC, the incremental cost-utility ratio was ₹35,962 per QALY gain with PGT test opting. In deterministic and probabilistic sensitivity analysis, the base case results were found to be insensitive to the variation in model parameters. In the cost-effectiveness-acceptability curve analysis, a 90% probability of cost-effectiveness was reached at a willingness-to-pay(WTP) of ₹ 71,630 well below one time GDP threshold of WTP used. CONCLUSION: Clinical efficacy and the cost-effectiveness of the warfarin pharmacogenetic test suggest its routine use as a point of care investigation for patient care in LMICs.

Cost-Effectiveness Analysis of Denosumab in the Prevention of Skeletal-Related Events Among Patients With Breast Cancer With Bone Metastasis in India.

PURPOSE: Denosumab is clinically superior to zoledronic acid (ZA) for preventing and delaying time to first and subsequent skeletal-related events (SREs) among patients with breast cancer (BC) with bone metastases. We evaluated the cost and health benefits of denosumab and ZA (once every 4 weeks and once every 12 weeks) among four different molecular subtypes of BC with bone metastases in India. MATERIALS AND METHODS: A Markov model was developed in Microsoft Excel to estimate lifetime health consequences and resulting costs among cohort of 1,000 patients with BC with bone metastasis, for three intervention scenarios, namely denosumab (once every 4 weeks), ZA (once every 4 weeks), and ZA (once every 12 weeks). The health outcomes were measured in terms of SREs averted and quality-adjusted life-years (QALYs) gained. The cost of each intervention scenario was measured using both the health system and the patient's perspectives. Indirect costs because of lost productivity were not included. The future costs and outcomes were discounted at the standard rate of 3%. RESULTS: Over a lifetime, the incremental number of SREs averted with use of denosumab once every 4 weeks (compared with ZA once every 4 weeks and once every 12 weeks) among patients with luminal A, luminal B, human epidermal growth factor receptor 2-enriched, and triple negative breast cancer were estimated as 0.39, 0.26, 0.25, and 0.19, respectively. The number of QALYs lived were slightly higher in the denosumab arm (1.45-2.80) compared with ZA once every 4 weeks and once every 12 weeks arms (1.44-2.78). However, denosumab once every 4 weeks was not found to be a cost-effective alternative for either of the four molecular subtypes of breast cancer. ZA once every 12 weeks was found to be a cost-effective option with an average cost-effectiveness ratio ranging between ₹68,254 and ₹73,636. CONCLUSION: ZA once every 12 weeks is the cost-effective treatment option for BC with bone metastases in India. The present study findings hold significance for standard treatment guidelines under India's government-funded health insurance program.